Environmentally Friendly Strategies for Formulating Vegetable Oil-Based Nanoparticles for Anticancer Medicine

Ci a ion: F ei e, N.; Ba bosa, R.d.M.; Ga cía-Villén, F.; Vise as, C.; Pe ioli, L.; Fialho, R.; Albuque que, E. En i onmen ally F iendly S a egies o Fo mula ing Vege able Oil-Based Nanopa icles o An icance Medicine. Pha maceu ics 2023,15, 1908. h ps://doi.o g/10.3390/ pha maceu ics15071908 Academic Edi o : Mon se a Colilla Recei ed: 24 May 2023 Re ised: 3 July 2023 Accep ed: 5 July 2023 Published: 8 July 2023 Copy igh : © 2023 by he au ho s. Licensee MDPI, Basel, Swi ze land. This a icle is an open access a icle dis ibu ed unde he e ms and condi ions o he C ea i e Commons A ibu ion (CC BY) license (h ps:// c ea i ecommons.o g/licenses/by/ 4.0/). pha maceu ics Re iew En i onmen ally F iendly S a egies o Fo mula ing Vege able Oil-Based Nanopa icles o An icance Medicine Na hália F ei e 1, Raquel de Melo Ba bosa 2,* , Fá ima Ga cía-Villén3, Césa Vise as 3,4 , Luana Pe ioli 5, Rosana Fialho 1and Elaine Albuque que 1 1G adua e P og am in Indus ial Enginee ing, Poly echnic School, Fede al Uni e si y o Bahia, Sal ado 40210-630, B azil; na halia ei as ei [email p o ec ed] (N.F.); [email p o ec ed] (R.F.); [email p o ec ed] (E.A.) 2Labo a o y o D ug De elopmen , Depa men o Pha macy, Fede al Uni e si y o Rio G ande do No e, Na al 59012-570, B azil 3Depa men o Pha macy and Pha maceu ical Technology, School o Pha macy, Uni e si y o G anada, Campus o Ca uja, 18071 G anada, Spain; ga illen@ug .es (F.G.-V.); c ise as@ug .es (C.V.) 4Andalusian Ins i u e o Ea h Sciences, CSIC-Uni e si y o G anada, A . de las Palme as 4, A milla, 18100 G anada, Spain 5Depa men o Pha maceu ic Science, Uni e si y o Pe ugia, 06123 Pe ugia, I aly; [email p o ec ed] *Co espondence: ba bosa@ug .es Abs ac : The de elopmen o g een syn hesized polyme ic nanopa icles wi h an icance s udies has been an eme ging ield in academia and he pha maceu ical and chemical indus ies. Vege able oils a e po en ial subs i u es o pe oleum de i a i es, as hey p esen a clean and en i onmen ally iendly al e na i e and a e a ailable in abundance a ela i ely low p ices. Biomass-de i ed chemicals can be con e ed in o monome s wi h a unique s uc u e, gene a ing ma e ials wi h new p ope ies o he syn hesis o sus ainable monome s and polyme s. The p oduc ion o bio-based polyme ic nanopa icles is a p omising applica ion o g een chemis y o biomedical uses. The e is an inc easing demand o biocompa ible and biodeg adable ma e ials o speci ic applica ions in he biomedical a ea, such as cance he apy. This is encou aging scien is s o wo k on esea ch owa d designing polyme s wi h enhanced p ope ies and clean p ocesses, con aining oncology ac i e pha maceu ical ing edien s (APIs). The nanoencapsula ion o hese APIs in bio-based polyme ic nanopa icles can con ol he elease o he subs ances, inc ease bioa ailabili y, educe p oblems o ola ili y and deg ada ion, educe side e ec s, and inc ease ea men e iciency. This e iew discusses he use o g een chemis y o bio-based nanopa icle p oduc ion and i s applica ion in an icance medicine. The use o cas o oil o he p oduc ion o enewable monome s and polyme s is p oposed as an ideal candida e o such applica ions, as well as mo e sui able me hods o he p oduc ion o bio-based nanopa icles and some oncology APIs a ailable o an icance applica ion. Keywo ds: g een chemis y; ege able oils; bio-based nanopa icles; oncology APIs 1. In oduc ion The polyme indus y plays a signi ican ole in ou socie y as polyme s ha e become essen ial ma e ials nowadays. Howe e , conce ns o e he ex ensi e use o ossil-based aw ma e ials, la ge amoun s o eagen s, and he accumula ion o polyme ic ma e ials in he en i onmen ha e inc eased. The need o elease he polyme indus y om i s depen- dence on deple ing esou ces is pushing he sea ch o indus ially applicable enewable al e na i es [1]. Ma e ials in he en i onmen p o ide scien is s and enginee s wi h he possibili y o change he polyme iza ion p ocess o de elop a mo e sus ainable socie y. Resea ch has ocused mainly on eplacing ossil aw ma e ials wi h enewable al e na i es and de eloping end-o -li e op ions ha gene a e ma e ials ha a e sui able o ecycling o biodeg ada ion [2]. Pha maceu ics 2023,15, 1908. h ps://doi.o g/10.3390/pha maceu ics15071908 h ps://www.mdpi.com/jou nal/pha maceu ics Pha maceu ics 2023,15, 1908 2 o 22 One sus ainable echnology is he applica ion o he p inciples o g een chemis y o a ious p ocesses. The design o chemical p oduc s and p ocesses ha educe o elimina e he use and gene a ion o haza dous subs ances is essen ial o li ing wi hou ha ing a nega i e impac on he en i onmen . The sus ainabili y e alua ion o a p oduc ’s c ea ion s a s om he analysis o he eeds ock used and i s ex ac ion. This highligh s he impo ance o he se en h p inciple o g een chemis y: “a aw ma e ial o eeds ock should be enewable a he han deple ing, whe e e echnically and economically p ac icable” [ 3 ]. A collabo a i e e o by indus y, academia, and he go e nmen is needed o p omo e he adop ion o he g een chemis y echnologies necessa y o achie e a sus ainable ci i- liza ion. The p og ess o chemis y esea ch, associa ed wi h he indus ial e olu ion, has c ea ed a new scope o he p epa a ion o no el polyme ic ma e ials based on enewable esou ces. Biomass-de i ed chemicals can be con e ed in o monome s wi h a unique s uc u e, p oducing ma e ials wi h no el p ope ies, o modi ied in o de o subs i u e comme cial pe oleum-based ones. Vege able oils exhibi nume ous eac i e si es sui able o unc ional- iza ion, including es e g oups and double bonds p esen in unsa u a ed a y acids, which can unde go chemical modi ica ions h ough ac yla ion, anses e i ica ion, me a hesis, and epoxida ion eac ions. These ans o ma ions enable he con e sion o iglyce ides in o monome s capable o polyme iza ion [4]. The mos commonly encoun e ed polyme iza ion echniques o bio-based monome s a e adical polyme iza ion, condensa ion polyme iza ion, and ca ionic polyme iza ion. These echniques ha e been employed o he syn hesis o di e se ege able oil-based polyme ypes, including polyes e s, polyamides, epoxies, and polyu e hanes [5]. The ab ica ion o polyme ic nanopa icles based on ege able oils o biomedical applica ions can be achie ed h ough a ious echniques. Among hese, miniemulsion polyme iza ion and sol en e apo a ion echniques a e widely ecognized and ci ed due o hei inhe en ad an ages, including p ocess simplici y and s abili y. Miniemulsion polyme iza ion is a he e ogeneous polyme iza ion p ocess used o he p oduc ion o polyme s in he o m o nanopa icles o di e en applica ions o polyme ic ma e ial. The hiol-ene eac ions can be used in polyme and monome syn hesis and modi ica ion, side-chain/end-g oup modi ica ion, and p epa a ion o a ious ypes o b anched mac omolecules. In he sol en e apo a ion echnique, polyme solu ions a e p epa ed in a ola ile sol en , and emulsions a e o mula ed. These kinds o polyme ic nanopa icles can be used in biomedical and pha maceu ical applica ions, such as an i umo he apy [1,6–8]. Nanopa icles ha e been o signi ican in e es o e he las decade as hey o e g ea bene i s o d ug deli e y o o e come limi a ions in con en ional chemo he apy o an icance ea men s, o example. Nanopa icles o use as an i umo d ug ca ie s ha e been in de elopmen due o hei many ad an ages such as p olonging he biological ci cula ion ime, minimizing non-speci ic up ake, p e en ing undesi able side e ec s, imp o ing cellula pene a ion, and allowing o speci ic cance a ge ing [9]. A conside able amoun o wo k has been conduc ed in sea ch o no el cance he apies using nanopa icle echnology. Combined ea men s employ ei he na u ally ac i e ing edi- en s o d ugs al eady in ended o o he uses so as o inc ease cell sensi i i y o he apy and educe d ug oxici y, using a pa icula pha maceu ical combina ion and nano echnology o de elop d ug deli e y sys ems o a ge ing d ugs o speci ic umo s [10]. This s udy aims o elucida e he applica ion o g een chemis y p inciples in he de elopmen o bio-based polyme ic nanopa icles o an icance he apy. Fu he mo e, i compiles he use o ege able oils as sou ces o enewable monome s and polyme s, highligh ing cas o oil as a p omising candida e o such pu poses. Addi ionally, i explo es mo e sui able me hodologies o he p oduc ion o bio-based nanopa icles and discusses a ious oncology ac i e pha maceu ical ing edien s (APIs) wi h po en ial o an icance applica ions. Pha maceu ics 2023,15, 1908 3 o 22 2. G een Chemis y: Monome s and Polyme s om Renewable Resou ces The e m g een chemis y, as adop ed by he IUPAC, is de ined as he in en ion, design, and applica ion o chemical p oduc s and p ocesses o educe o elimina e he use and gene a ion o haza dous subs ances. Since hei ini ial appea ance in he scien i ic li e a u e, he e ms “g een” and “sus ainable” ha e been inc easingly used and a e nowadays p esen in se e al esea ch a eas. G een chemis y may be conside ed in he scien i ic and economical con ex in which academia, indus y, and go e nmen a e a emp ing o con e ge hei e o s o he de el- opmen o a sus ainable ci iliza ion [11]. G een chemis y, also called sus ainable chemis y, da es om 1991 when he U.S. En i onmen al P o ec ion Agency (EPA) launched he Al e na i e Syn he ic Pa hways o Pollu ion P e en ion esea ch p og am unde he auspices o he Pollu ion P e en ion Ac o 1990. Howe e , he name g een chemis y was o icially adop ed in 1996. Ame ican chemis Paul Anas as, one o he p incipal ounde s o g een chemis y, claimed ha by imp o ing how chemicals a e syn hesized, i migh be possible o p e- en he p oduc ion o pollu an s. Toge he wi h John Wa ne in 1998, hey c ea ed g een chemis y’s 12 p inciples, including p e en ing was e whe e e possible, designing chem- icals ha b eak down in o ha mless p oduc s a e hey a e used, o using enewable eeds ocks [12]. Fossil oil is consumed bo h in supplying ene gy as well as in he p oduc ion o chemicals and polyme s. I s ex ensi e exploi a ion o e he las 60 yea s has led o he cos -e ec i e and easy c ea ion o e e yday p oduc s. The inc ease in wo ld popula ion and economic de elopmen , along wi h he dec ease in he economically a ailable amoun o ossil oil, highligh he issue o i s ini e a ailabili y. Wi h a egene a ion ime o se e al million yea s, ossil esou ces a e ex ac ed and con- sumed as e han hey a e p oduced and a e hus conside ed non- enewable. Fu he mo e, en i onmen al conce ns ela ed o hei p oduc ion and use, such as g eenhouse gas emis- sions and he disposal o hese non-deg adable ma e ials ha led o se ious en i onmen al pollu ion, now mo i a e esea che s o de elop sus ainable solu ions [3,13]. The p og ess o chemis y esea ch, associa ed wi h he indus ial e olu ion, has c ea ed a new scope o he p epa a ion o no el polyme ic ma e ials based on enewable esou ces, i s h ough he chemical modi ica ion o na u al polyme s om he mid- nine een h cen u y, which ga e ise o he i s comme cial he moplas ic ma e ials, such as cellulose ace a e and ni a e and he i s elas ome s, and second h ough he ulcaniza ion o na u al ubbe . La e , hese p ocesses we e complemen ed by app oaches based on he con olled polyme iza ion o a a ie y o na u al monome s and oligome s [14]. The use o enewable aw ma e ials, aking ad an age o he syn he ic po en ial o na u e, can mee o he p inciples o g een chemis y, such as a buil -in design o deg ada ion o an expec ed lowe oxici y o he esul ing p oduc s [ 15 ]. Biomass-de i ed chemicals can be ei he con e ed in o monome s wi h unique s uc u es, leading o ma e ials wi h no el p ope ies, o modi ied in o de o mimic comme cial pe oleum- based key molecules and monome s. Some o he mos widely applied enewable aw ma e ials in he chemical indus y include plan oils, polysaccha ides, suga s, wood, and o he s. Fo ins ance, ca bon dioxide is copolyme ized wi h p opylene oxide o gene a e p opylene ca bona e polyols. Te penes, such as limonene, a e chemically ans o med o limonene oxide and copolyme ized wi h ca bon dioxide o gene a e poly(limonene ca bona e). T iglyce ides, om ege able oils, a e ans o med in o long-chain alipha ic polyes e s. Na u al ca bohyd a e polyme s, such as s a ch, a e b oken down o glucose, which is subsequen ly ans o med in o polyme s such as poly(e hylene u oa e), poly- lac ide, bio-de i ed poly(e hylene e eph hala e), o bio-de i ed polye hylene. P oduc s ob ained om hese enewables a e as di e se as pha maceu icals, coa ings, packaging ma e ials, o ine chemicals [2,3,15]. Pha maceu ics 2023,15, 1908 4 o 22 Vege able oils ep esen one o he mos in e es ing classes o enewables o he syn hesis o sus ainable monome s and polyme s, as hey a e abundan and ha e ela i ely low p ices, making hem indus ially a ac i e. Thei long alipha ic chain con ibu es as a majo elemen o he polyme backbone [1,3,15]. Biodeg adable polyme s a e de ined as polyme s ha a e deg aded and ca abolized, e en ually o ca bon dioxide and wa e , by na u ally occu ing mic oo ganisms such as bac e ia, ungi, o algae. In addi ion, when hey a e deg aded, hese polyme s should no gene a e any subs ances ha a e ha m ul o he na u al en i onmen . Gene ally, na u al ma e ials o syn he ic polyme s ha con ain hyd olyzable bonds in he backbone, such as polyamides, polyes e s, and polye he , a e in e es ing candida es o biodeg ada ion. Se e al pa ame e s ha e been epo ed o in luence he deg ada ion beha io o biodeg adable polyme s, such as he chemical composi ion, molecula weigh , and c ys- allini y o he polyme . Al hough he biodeg adabili y o a ma e ial is independen o he o igin o he s a ing aw ma e ials used, biomass ep esen s an abundan enewable esou ce o he p oduc ion o biodeg adable ma e ials [13]. 3. Syn hesis o Monome s om Vege able Oils Vege able oils a e his o ically and cu en ly he mos impo an enewable eeds ock o he chemical indus y [ 16 ]. Due o hei uni e sal a ailabili y, inhe en biodeg adabili y, and low p ice, ege able oils ha e become an a ea o in ensi e in e es o bo h academic and indus ial esea ch as pla o m chemicals o polyme ic ma e ials [17]. The majo componen s o ege able oils a e iglyce ides ( i-es e s o glyce ol wi h long-chain a y acids) wi h a ying composi ions o a y acids depending on he plan , he c op, he season, and he g owing condi ions [ 15 ]. Vege able iglyce ides a e among he mos enewable esou ces exploi ed in science, in addi ion o o he easons, because o hei unsa u a ed a ie ies [ 14 ]. The gene al molecula s uc u e o iglyce ides is demons a ed in Figu e 1. Pha maceu ics 2023, 15, x FOR PEER REVIEW 4 o 22 ca bona e). T iglyce ides, om ege able oils, a e ans o med in o long-chain alipha ic polyes e s. Na u al ca bohyd a e polyme s, such as s a ch, a e b oken down o glucose, which is subsequen ly ans o med in o polyme s such as poly(e hylene u oa e), polylac ide, bio-de i ed poly(e hylene e eph hala e), o bio-de i ed polye hylene. P od- uc s ob ained om hese enewables a e as di e se as pha maceu icals, coa ings, packag- ing ma e ials, o ine chemicals [2,3,15]. Vege able oils ep esen one o he mos in e es ing classes o enewables o he syn- hesis o sus ainable monome s and polyme s, as hey a e abundan and ha e ela i ely low p ices, making hem indus ially a ac i e. Thei long alipha ic chain con ibu es as a majo elemen o he polyme backbone [1,3,15]. Biodeg adable polyme s a e de ined as polyme s ha a e deg aded and ca abolized, e en ually o ca bon dioxide and wa e , by na u ally occu ing mic oo ganisms such as bac e ia, ungi, o algae. In addi ion, when hey a e deg aded, hese polyme s should no gene a e any subs ances ha a e ha m ul o he na u al en i onmen . Gene ally, na u al ma e ials o syn he ic polyme s ha con ain hyd olyzable bonds in he backbone, such as polyamides, polyes e s, and polye he , a e in e es ing candida es o biodeg ada ion. Se e al pa ame e s ha e been epo ed o in luence he deg ada ion beha io o bio- deg adable polyme s, such as he chemical composi ion, molecula weigh , and c ys al- lini y o he polyme . Al hough he biodeg adabili y o a ma e ial is independen o he o igin o he s a ing aw ma e ials used, biomass ep esen s an abundan enewable e- sou ce o he p oduc ion o biodeg adable ma e ials [13]. 3. Syn hesis o Monome s om Vege able Oils Vege able oils a e his o ically and cu en ly he mos impo an enewable eeds ock o he chemical indus y [16]. Due o hei uni e sal a ailabili y, inhe en biodeg adabil- i y, and low p ice, ege able oils ha e become an a ea o in ensi e in e es o bo h aca- demic and indus ial esea ch as pla o m chemicals o polyme ic ma e ials [17]. The majo componen s o ege able oils a e iglyce ides ( i-es e s o glyce ol wi h long-chain a y acids) wi h a ying composi ions o a y acids depending on he plan , he c op, he season, and he g owing condi ions [15]. Vege able iglyce ides a e among he mos enewable esou ces exploi ed in science, in addi ion o o he easons, because o hei unsa u a ed a ie ies [14]. The gene al molecula s uc u e o iglyce ides is demons a ed in Figu e 1. Figu e 1. S uc u e o a polyunsa u a ed iglyce ide. Al hough iglyce ides a e ound in almos all plan s, he quan i y ha is a ailable a ies; o example, c ops such as soybeans a e es ima ed o yield only 20 w % o iglyc- e ides. Ano he challenge is ha he chemical composi ions o iglyce ides a y bo h be- ween and wi hin a pa icula c op [2]. The physical and chemical p ope ies o ege able oils a e mainly de e mined by he a y acid chain leng h and he numbe s and loca ions o double bonds in he a y acid chains. The leng h o he a y chain is usually be ween C12 and C20, wi h oleic acid (C18:1), linoleic acid (C18:2), and linolenic acid (C18:3) being he mos common [17]. Figu e 1. S uc u e o a polyunsa u a ed iglyce ide. Al hough iglyce ides a e ound in almos all plan s, he quan i y ha is a ailable a ies; o example, c ops such as soybeans a e es ima ed o yield only 20 w % o iglyc- e ides. Ano he challenge is ha he chemical composi ions o iglyce ides a y bo h be ween and wi hin a pa icula c op [2]. The physical and chemical p ope ies o ege able oils a e mainly de e mined by he a y acid chain leng h and he numbe s and loca ions o double bonds in he a y acid chains. The leng h o he a y chain is usually be ween C12 and C20, wi h oleic acid (C18:1), linoleic acid (C18:2), and linolenic acid (C18:3) being he mos common [17]. The a y acids accoun o 95% o he o al weigh o iglyce ides, and hei con en is cha ac e is ic o each plan oil. The s uc u es o some equen ly s udied a y acids a e depic ed in Figu e 2. Pha maceu ics 2023,15, 1908 5 o 22 Pha maceu ics 2023, 15, x FOR PEER REVIEW 5 o 22 The a y acids accoun o 95% o he o al weigh o iglyce ides, and hei con en is cha ac e is ic o each plan oil. The s uc u es o some equen ly s udied a y acids a e depic ed in Figu e 2. Figu e 2. Fa y acids commonly used in polyme chemis y: (a) oleic acid, (b) linoleic acid, (c) lino- lenic acid, (d) e ucic acid, (e) pe oselinic acid, ( ) icinoleic acid, (g) e nolic acid, (h) 10-undecenoic acid. Fa y acids and es e s can be easily ob ained ei he by simple hyd olysis o alcoholy- sis o iglyce ides. They a e aluable enewable building blocks o he syn hesis o de- signed monome s in he sea ch o speci ic polyme p ope ies ha do no equi e ex en- si e chemical modi ica ion p io o hei applica ion. The e is a g owing in e es in he use o a y acids as p ecu so s o monome s, no only because o hei enewabili y bu also because o he p ope ies hey can p o ide o he inal molecule [5]. The mos common oil used in his kind o s udy is cas o oil, due o he p esence o hyd oxyl g oup, and soybean oil, due o i s low cos and high a ailabili y. Cas o oil is a e y e sa ile enewable eeds ock o all kinds o polyme ic ma e ials, including polyes- e s, polyamides, polyu e hanes, and many o he s. A p ocess ha has conside able po en- ial is eac ing o he alkene g oups ound in unsa u a ed a y es e s o p oduce α, ω- diene o α,ω-diols. Me hyl 10-undecenoic acid, a cas o oil-de i ed subs ance, was shown o be a sui able s a ing ma e ial o he p epa a ion o es e s wi h alkene g oups ha can p oduce biodeg adable polyme s [18]. 4. Cas o Oil as a Renewable Raw Ma e ial Cas o oil, om he cas o plan (Ricinus communis), a na i e o opical Asia and A - ica, is one o he mos exploi ed ege able oils as a aw ma e ial o he chemical indus y. Figu e 2. Fa y acids commonly used in polyme chemis y: ( a ) oleic acid, ( b ) linoleic acid, ( c ) linolenic acid, ( d ) e ucic acid, ( e ) pe oselinic acid, ( ) icinoleic acid, ( g ) e nolic acid, ( h ) 10-undecenoic acid. Fa y acids and es e s can be easily ob ained ei he by simple hyd olysis o alcoholysis o iglyce ides. They a e aluable enewable building blocks o he syn hesis o designed monome s in he sea ch o speci ic polyme p ope ies ha do no equi e ex ensi e chemical modi ica ion p io o hei applica ion. The e is a g owing in e es in he use o a y acids as p ecu so s o monome s, no only because o hei enewabili y bu also because o he p ope ies hey can p o ide o he inal molecule [5]. The mos common oil used in his kind o s udy is cas o oil, due o he p esence o hyd oxyl g oup, and soybean oil, due o i s low cos and high a ailabili y. Cas o oil is a e y e sa ile enewable eeds ock o all kinds o polyme ic ma e ials, including polyes e s, polyamides, polyu e hanes, and many o he s. A p ocess ha has conside able po en ial is eac ing o he alkene g oups ound in unsa u a ed a y es e s o p oduce α , ω -diene o α , ω -diols. Me hyl 10-undecenoic acid, a cas o oil-de i ed subs ance, was shown o be a sui able s a ing ma e ial o he p epa a ion o es e s wi h alkene g oups ha can p oduce biodeg adable polyme s [18]. 4. Cas o Oil as a Renewable Raw Ma e ial Cas o oil, om he cas o plan (Ricinus communis), a na i e o opical Asia and A ica, is one o he mos exploi ed ege able oils as a aw ma e ial o he chemical indus y. I is na u alized and cul i a ed on a comme cial scale all a ound he wo ld in empe a e zones. Like o he plan oils, cas o oil is ex ac ed by a a ie y o p ocesses o a combina ion o p ocesses, such as di e en p essu es and sol en ex ac ion ollowed by a e ining p ocess. Pha maceu ics 2023,15, 1908 6 o 22 The a y acids o cas o oil consis o up o 90% icinoleic acid and a ying small amoun s o sa u a ed and unsa u a ed a y acids such as oleic acid, linoleic acid, and linolenic acid. The high con en o icinoleic acid is he eason o he high alue o cas o oil and i s e sa ile applica ion possibili ies in he chemical indus y. F om cas o oil p ocessing, like om o he applica ions o ege able oils, glyce ol is ob ained as a byp oduc , which is a pla o m chemical wi h widesp ead applica ion possibili ies in cosme ics, pha maceu icals, de e gen s, he p oduc ion o esins and addi i es, and he ood indus y [ 19 ]. Fo ins ance, ce ain cha ac e is ics o cas o oil, namely high lub ici y, high iscosi y o e a wide ange o empe a u es, and insolubili y in alipha ic pe ochemical uels and sol en s, make i di ec ly applicable as a lub ican , coa ing, ink, polyme , and oam. Bio echnology o e s ways o al e he composi ion o cas o oil a y acids o p ocesses in he chemical indus y wi h an emphasis on de elopmen and applica ion in polyme science. The e a e se e al possible chemical ans o ma ions o cas o oil depending on he eac ing unc ional g oup. Es e eac ions include hyd olysis, es e i ica ion, alcoholysis, saponi ica ion, educ ion, amida ion, and halogena ion; double bond eac ions include oxida ion, polyme iza ion, hyd ogena ion, epoxida ion, halogena ion, addi ion eac ions, sul ona ion, and me a hesis; and hyd oxyl g oup eac ions include dehyd a ion, hyd olysis, caus ic usion, py olysis, alkoxyla ion, es e i ica ion, halogena ion, u e hane o ma ion, and sul ona ion [20]. The py olysis o icinoleic acid a high empe a u es (>350 ◦ C) spli s he icinolea e molecule a he hyd oxyl g oup o o m hep aldehyde and undecenoic acid (Figu e 3), which is a pla o m chemical ha can be used o syn hesize a la ge a ie y o enewable monome s and polyme s [20–22]. Pha maceu ics 2023, 15, x FOR PEER REVIEW 6 o 22 I is na u alized and cul i a ed on a comme cial scale all a ound he wo ld in empe a e zones. Like o he plan oils, cas o oil is ex ac ed by a a ie y o p ocesses o a combina- ion o p ocesses, such as diffe en p essu es and sol en ex ac ion ollowed by a e ining p ocess. The a y acids o cas o oil consis o up o 90% icinoleic acid and a ying small amoun s o sa u a ed and unsa u a ed a y acids such as oleic acid, linoleic acid, and lin- olenic acid. The high con en o icinoleic acid is he eason o he high alue o cas o oil and i s e sa ile applica ion possibili ies in he chemical indus y. F om cas o oil p ocessing, like om o he applica ions o ege able oils, glyce ol is ob ained as a byp oduc , which is a pla o m chemical wi h widesp ead applica ion possibili ies in cosme ics, pha maceu i- cals, de e gen s, he p oduc ion o esins and addi i es, and he ood indus y [19]. Fo ins ance, ce ain cha ac e is ics o cas o oil, namely high lub ici y, high iscosi y o e a wide ange o empe a u es, and insolubili y in alipha ic pe ochemical uels and sol en s, make i di ec ly applicable as a lub ican , coa ing, ink, polyme , and oam. Bio echnology offe s ways o al e he composi ion o cas o oil a y acids o p o- cesses in he chemical indus y wi h an emphasis on de elopmen and applica ion in pol- yme science. The e a e se e al possible chemical ans o ma ions o cas o oil depending on he eac ing unc ional g oup. Es e eac ions include hyd olysis, es e i ica ion, alco- holysis, saponi ica ion, educ ion, amida ion, and halogena ion; double bond eac ions in- clude oxida ion, polyme iza ion, hyd ogena ion, epoxida ion, halogena ion, addi ion e- ac ions, sul ona ion, and me a hesis; and hyd oxyl g oup eac ions include dehyd a ion, hyd olysis, caus ic usion, py olysis, alkoxyla ion, es e i ica ion, halogena ion, u e hane o ma ion, and sul ona ion [20]. The py olysis o icinoleic acid a high empe a u es (>350 °C) spli s he icinolea e molecule a he hyd oxyl g oup o o m hep aldehyde and undecenoic acid (Figu e 3), which is a pla o m chemical ha can be used o syn hesize a la ge a ie y o enewable monome s and polyme s [20–22]. Figu e 3. P oduc s o he he mal agmen a ion o icinoleic acid. (1) Ricinoleic acid, (2) 10-unde- cenoic acid, (3) hep anal. The use o cas o oils as a aw ma e ial in he syn hesis o polyme ic ma e ials is e y well-es ablished. Cas o oil polyme s a e applied in a ious ields such as wound d ess- ing, d ug deli e y, bone issue enginee ing, and memb anes o uel cell ab ica ion [23]. A as a ay o copolyme s is iable when cas o oil (o icinoleic acid) is combined wi h o he monome s. Ma e ials wi h a ied p ope ies can be ob ained by weaking he chemis y o hese copolyme s. Al e ing o comonome composi ions leads o polyes e s wi h con olled mechanical, he mal, and iscoelas ic p ope ies, as well as deg ada ion p o iles [24]. Re . [25] syn hesized a bio-based monome ac yla e icinoleic acid om cas o oil and copolyme ized i wi h me hyl me hac yla e in miniemulsion, o ming polyme ic nanopa - icles. The addi ion o he bio-based monome led o a dec ease in he glass ansi ion Figu e 3. P oduc s o he he mal agmen a ion o icinoleic acid. (1) Ricinoleic acid, (2) 10- undecenoic acid, (3) hep anal. The use o cas o oils as a aw ma e ial in he syn hesis o polyme ic ma e ials is e y well-es ablished. Cas o oil polyme s a e applied in a ious ields such as wound d essing, d ug deli e y, bone issue enginee ing, and memb anes o uel cell ab ica ion [23]. A as a ay o copolyme s is iable when cas o oil (o icinoleic acid) is combined wi h o he monome s. Ma e ials wi h a ied p ope ies can be ob ained by weaking he chemis y o hese copolyme s. Al e ing o comonome composi ions leads o polyes e s wi h con olled mechanical, he mal, and iscoelas ic p ope ies, as well as deg ada ion p o iles [24]. Re . [ 25 ] syn hesized a bio-based monome ac yla e icinoleic acid om cas o oil and copolyme ized i wi h me hyl me hac yla e in miniemulsion, o ming polyme ic nanopa icles. The addi ion o he bio-based monome led o a dec ease in he glass ansi ion empe a u e o he copolyme and o he o ma ion o a small ac ion o gel, esul ing in ma e ials wi h in e es ing p ope ies o u u e applica ions, such as p essu e- sensi i e adhesi es. In he medical ield, biodeg adable alipha ic polyes e s a e he p e e ed ma e ials as bioma e ials because o hei biodeg ada ion and biocompa ibili y. Re . [ 26 ] ob ained Pha maceu ics 2023,15, 1908 7 o 22 biocompa ible polyme ic nanopa icles ia hiol-ene polyme iza ion in miniemulsion us- ing a ully enewable α , ω -diene monome ob ained om 10-undecenoic acid and 1,3- p opanediol; bo h we e de i ed om cas o oil. Addi ionally, in he biomedical applica ion o polyme s nanopa icles, Re . [ 27 ] syn- hesized poly( hioe he -es e ) nanopa icles ia hiol-ene miniemulsion polyme iza ion using a bio-based α , ω -diene monome , namely dianhyd o-d-gluci yl diundec-10-enoa e, syn hesized om 10-undecenoic acid (de i ed om cas o oil) and isoso bide (de i ed om s a ch). These kinds o polyme nanopa icles ha e emendous scope o u he ab ica ion o he biomedical applica ion a ea, including s udies o an icance ea men s. 5. Polyme ic Nanopa icles and Some P oduc ion Techniques Nanopa icles a e equen ly de ined as solid, colloidal pa icles in he ange o 10– 1000 nm. This is a collec i e e m gi en o any ype o polyme nanopa icle, bu speci ically o nanosphe es and nanocapsules. Nanocapsules ac as d ug ese oi s due o hei esicula s uc u e, in which he e ained ac i e pha maceu ical ing edien s a e ese ed in an aqueous o non-aqueous liquid co e placed in he esicle ca i y and enclosed by he solidi ied polyme ic shell. While nanosphe es a e ma ix pa icles, pa icles whose en i e mass is solid and molecules may be adso bed a he sphe e su ace o encapsula ed wi hin he pa icle [8,28]. The ield o polyme nanopa icles assumes a signi ican ole ac oss a b oad spec um o disciplines, encompassing elec onics [ 29 ], conduc ing ma e ials [ 30 ], medicine [ 31 , 32 ], and bio echnology [33,34]. Polyme s a e e y con enien ma e ials o he p oduc ion o nanopa icles wi h many po en ial medical applica ions. The polyme s used in he p epa a ion o nanopa icles should be compa ible wi h he body in e ms o adap abili y and biodeg adabili y. The mos commonly used na u al polyme s in he p epa a ion o polyme ic nanopa icles a e chi osan, gela in, sodium algina e, and albumin. Syn he ic polyme s a e mos ly ep e- sen ed by polylac ides (PLAs), polyglycolides (PGAs), poly (lac ide co-glycolides) (PLGAs), polyanhyd ides, polyo hoes e s, polycyanoac yla es, polycap olac one, poly glu amic acid, poly malic acid, poly (N- inyl py olidone), poly (me hyl me hac yla e), poly ( inyl alcohol), poly (ac ylic acid), poly ac ylamide, poly (e hylene glycol), and poly (me hac ylic acid). Al hough he e a e many possible polyme s, he applica ion o he de i a i es o cas- o oil, such as 10-undecenoic acid, o he p epa a ion o monome s used in he p oduc ion o polyme nanopa icles has inc eased [28,34]. Polyme nanopa icles can be con enien ly p epa ed ei he om p e o med polyme s o he di ec polyme iza ion o monome s using classical mechanisms. Me hods such as sol- en e apo a ion [ 35 ], sal ing-ou [ 36 ], dialysis [ 37 ], and supe c i ical luid echnology [ 38 ] can be u ilized o he p epa a ion o polyme nanopa icles om p e o med polyme s. On he o he hand, polyme nanopa icles can be di ec ly syn hesized by he poly- me iza ion o monome s using a ious polyme iza ion echniques such as mic oemulsion, miniemulsion, and in e acial polyme iza ion (Figu e 4) [8]. 5.1. Sol en E apo a ion Technique The emulsi ica ion sol en e apo a ion echnique was i s epo ed in 1981 [ 39 ]. Hyd ophobic polyme s (syn he ic, semi-syn he ic, o na u al) and d ugs (usually lipophilic) a e dissol ed in an o ganic sol en (e.g., chlo o o m, dichlo ome hane, e hyl ace a e), which is ola ile and wa e -immiscible. This solu ion is hen emulsi ied in an aqueous s abilize solu ion. Emulsi ica ion is ca ied ou by sonica ion o unde high-ene gy homogeniza ion o educe he size o he emulsion d ople s, and an emulsion is o med. The o ganic sol en is hen emo ed by e apo a ion a oom empe a u e unde s i ing o unde educed p essu e. A e wa d, he solidi ied nanopa icles can be collec ed by ul acen i uga ion and washed wi h dis illed wa e o emo e addi i es, such as su ac an s (Figu e 5) [8,39–42]. Pha maceu ics 2023,15, 1908 8 o 22 Pha maceu ics 2023, 15, x FOR PEER REVIEW 8 o 22 Figu e 4. Schema ic ep esen a ion o a ious echniques o he p epa a ion o polyme nanopa i- cles. 5.1. Sol en E apo a ion Technique The emulsi ica ion sol en e apo a ion echnique was i s epo ed in 1981 [39]. Hy- d ophobic polyme s (syn he ic, semi-syn he ic, o na u al) and d ugs (usually lipophilic) a e dissol ed in an o ganic sol en (e.g., chlo o o m, dichlo ome hane, e hyl ace a e), which is ola ile and wa e -immiscible. This solu ion is hen emulsi ied in an aqueous s abilize solu ion. Emulsi ica ion is ca ied ou by sonica ion o unde high-ene gy ho- mogeniza ion o educe he size o he emulsion d ople s, and an emulsion is o med. The o ganic sol en is hen emo ed by e apo a ion a oom empe a u e unde s i ing o unde educed p essu e. A e wa d, he solidi ied nanopa icles can be collec ed by ul a- cen i uga ion and washed wi h dis illed wa e o emo e addi i es, such as su ac an s (Figu e 5) [8,39–42]. Figu e 5. Scheme o he emulsi ica ion sol en e apo a ion echnique. Figu e 4. Schema ic ep esen a ion o a ious echniques o he p epa a ion o polyme nanopa icles. Pha maceu ics 2023, 15, x FOR PEER REVIEW 8 o 22 Figu e 4. Schema ic ep esen a ion o a ious echniques o he p epa a ion o polyme nanopa i- cles. 5.1. Sol en E apo a ion Technique The emulsi ica ion sol en e apo a ion echnique was i s epo ed in 1981 [39]. Hy- d ophobic polyme s (syn he ic, semi-syn he ic, o na u al) and d ugs (usually lipophilic) a e dissol ed in an o ganic sol en (e.g., chlo o o m, dichlo ome hane, e hyl ace a e), which is ola ile and wa e -immiscible. This solu ion is hen emulsi ied in an aqueous s abilize solu ion. Emulsi ica ion is ca ied ou by sonica ion o unde high-ene gy ho- mogeniza ion o educe he size o he emulsion d ople s, and an emulsion is o med. The o ganic sol en is hen emo ed by e apo a ion a oom empe a u e unde s i ing o unde educed p essu e. A e wa d, he solidi ied nanopa icles can be collec ed by ul a- cen i uga ion and washed wi h dis illed wa e o emo e addi i es, such as su ac an s (Figu e 5) [8,39–42]. Figu e 5. Scheme o he emulsi ica ion sol en e apo a ion echnique. Figu e 5. Scheme o he emulsi ica ion sol en e apo a ion echnique. Sol en e apo a ion is he mos commonly used echnique o he p epa a ion o he nanopa icles o polyme s in he cu en li e a u e on echniques using a dispe sion o p e o med polyme s [ 43 – 45 ]. In he polyme iza ion o monome s, he numbe o publica- ions on miniemulsion polyme iza ion and he de elopmen o a wide ange o enewable polyme ma e ials has ecen ly inc eased subs an ially [8]. 5.2. Miniemulsion Polyme iza ion Miniemulsion is pa o he emulsi ied polyme iza ion sys ems, and i s main cha ac- e is ic is he size o he d ops and he s abili y o he inal emulsion. A nanoemulsion can Pha maceu ics 2023,15, 1908 9 o 22 be conside ed a con en ional emulsion con aining e y small pa icles (size anging om 50 o 500 nm) [46,47]. Re . [48] we e pionee s in he s udy o polyme iza ions in miniemulsions, desc ibing he polyme iza ion p ocess in monome d ops. Thei discussions led o specula ion abou he possibili y o nuclea ion and polyme iza ion in e y small monome d ople s du ing emulsion polyme iza ion. Asua (2002) de ined miniemulsions as dispe sions o small monome d ops in wa e , s abilized by a su ac an agains he coalescence o he d ops by he ac ion o he B ownian mo ion (a union o wo o mo e d ops occu ing he up u e o he in e ace and esul ing in a la ge d op) and a co-s abilize o minimize di usional deg ada ion (Os wald Ripening, a p ocess in which small d ops a e g ouped by he di e ence o p essu e, leads o an inc ease in he a e age size o d ople s) [49]. A ypical o mula ion includes wa e , a monome , co-s abilizing (when used), a su ac- an , and an ini ia o (which can be soluble in he aqueous o o ganic phase). The su ac an is dissol ed in wa e , he ac i e o be encapsula ed is dissol ed in he monome , and bo h a e mixed unde agi a ion. A shea mechanism (homogeniza ion) is equi ed o ensu e he submic ome ic size o he d ops [46]. The mechanical homogeniza ion o miniemulsions can be ob ained by di e en me h- ods. Ini ially, simple agi a ion was used as he main means o homogeniza ion. Subse- quen ly, he use o omni-mixe s and ul a- u ax was ca aloged. Howe e , he ene gy ans e ed by hese echniques is no enough o ob ain small d ops dis ibu ed homo- geneously. Much highe ene gy o he agmen a ion o la ge d ops in o small ones is equi ed. Cu en ly, ul asonica ion is used, especially o he homogeniza ion o small quan i ies, while mic o-co uga o s o high-p essu e homogenize s a e a o able o la ge quan i ies o emulsion [46]. In he i s s age o he miniemulsion polyme iza ion p ocess, small d ops a e o med by a sys em con aining he dispe sed phase (a monome , ac i e o be encapsula ed, and a co-s abilize ) and con inuous phase (aqueous phase wi h a su ac an ). The ini ia o can be added in he dispe sed phase o con inuous phase, depending on whe he i is hyd o- o o ganic-soluble. The su ace a ea o he d ople s in hese sys ems is e y la ge, and mos su ac an is adso bed on he su ace o he d ople s [ 50 ]. In he second s ep, he d ops a e nuclea ed and polyme ized [ 51 , 52 ]. In Figu e 6, he scheme o he miniemulsion polyme iza ion p ocess is demons a ed. Pha maceu ics 2023, 15, x FOR PEER REVIEW 9 o 22 Sol en e apo a ion is he mos commonly used echnique o he p epa a ion o he nanopa icles o polyme s in he cu en li e a u e on echniques using a dispe sion o p e o med polyme s [43–45]. In he polyme iza ion o monome s, he numbe o publica- ions on miniemulsion polyme iza ion and he de elopmen o a wide ange o enewable polyme ma e ials has ecen ly inc eased subs an ially [8]. 5.2. Miniemulsion Polyme iza ion Miniemulsion is pa o he emulsi ied polyme iza ion sys ems, and i s main cha ac- e is ic is he size o he d ops and he s abili y o he inal emulsion. A nanoemulsion can be conside ed a con en ional emulsion con aining e y small pa icles (size anging om 50 o 500 nm) [46,47]. Re . [48] we e pionee s in he s udy o polyme iza ions in miniemulsions, desc ibing he polyme iza ion p ocess in monome d ops. Thei discussions led o specula ion abou he possibili y o nuclea ion and polyme iza ion in e y small monome d ople s du ing emulsion polyme iza ion. Asua (2002) de ined miniemulsions as dispe sions o small monome d ops in wa e , s abilized by a su ac an agains he coalescence o he d ops by he ac ion o he B own- ian mo ion (a union o wo o mo e d ops occu ing he up u e o he in e ace and e- sul ing in a la ge d op) and a co-s abilize o minimize diffusional deg ada ion (Os wald Ripening, a p ocess in which small d ops a e g ouped by he diffe ence o p essu e, leads o an inc ease in he a e age size o d ople s) [49]. A ypical o mula ion includes wa e , a monome , co-s abilizing (when used), a su - ac an , and an ini ia o (which can be soluble in he aqueous o o ganic phase). The su - ac an is dissol ed in wa e , he ac i e o be encapsula ed is dissol ed in he monome , and bo h a e mixed unde agi a ion. A shea mechanism (homogeniza ion) is equi ed o ensu e he submic ome ic size o he d ops [46]. The mechanical homogeniza ion o miniemulsions can be ob ained by diffe en me hods. Ini ially, simple agi a ion was used as he main means o homogeniza ion. Sub- sequen ly, he use o omni-mixe s and ul a- u ax was ca aloged. Howe e , he ene gy ans e ed by hese echniques is no enough o ob ain small d ops dis ibu ed homoge- neously. Much highe ene gy o he agmen a ion o la ge d ops in o small ones is e- qui ed. Cu en ly, ul asonica ion is used, especially o he homogeniza ion o small quan i ies, while mic o-co uga o s o high-p essu e homogenize s a e a o able o la ge quan i ies o emulsion [46]. In he i s s age o he miniemulsion polyme iza ion p ocess, small d ops a e o med by a sys em con aining he dispe sed phase (a monome , ac i e o be encapsula ed, and a co-s abilize ) and con inuous phase (aqueous phase wi h a su ac an ). The ini ia o can be added in he dispe sed phase o con inuous phase, depending on whe he i is hyd o- o o ganic-soluble. The su ace a ea o he d ople s in hese sys ems is e y la ge, and mos su ac an is adso bed on he su ace o he d ople s [50]. In he second s ep, he d ops a e nuclea ed and polyme ized [51,52]. In Figu e 6, he scheme o he miniemulsion polyme iza ion p ocess is demons a ed. Figu e 6. Scheme o he miniemulsion p ocess. Sou ce: adap ed om [51]. Figu e 6. Scheme o he miniemulsion p ocess. Sou ce: adap ed om [51]. 6. Thiol-Ene Polyme iza ion o Nanopa icle P oduc ion Thiol chemis y, a e sa ile ool, was i s desc ibed in 1905 by Posne . The au ho epo s he hiol coupling o di e en ypes o mono- and bi-unsa u a ed compounds such as alipha ics, a oma ics, e penes, and hyd oa oma ics. The hiol-ene ee adical addi ion is o special in e es due o i s applica ion ange and simplici y. Ea ly wo k in his ield appea ed in he la e-1930s o ea ly-1950s [53]. A pa en conce ning he polyme iza ion o di hiols and dialkenes ia adical addi ions da es back o 1941. The eac ion is well-known o p oceed ia a ee- adical mechanism. Pha maceu ics 2023,15, 1908 16 o 22 7. Machado, F.; Lima, E.L.; Pin o, J.C. A Re iew on Suspension Polyme iza ion P ocesses. Polime os 2007,17, 166–179. [C ossRe ] 8. Rao, J.P.; Geckele , K.E. Polyme Nanopa icles: P epa a ion Techniques and Size-Con ol Pa ame e s. P og. Polym. Sci. 2011 ,36, 887–913. [C ossRe ] 9. Nguyen, K.T. Ta ge ed Nanopa icles o Cance The apy:P omises and Challenges. J. Nanomed. Nano echnol. 2011 ,2, 1000103e. [C ossRe ] 10. Piccolo, M.; Menale, C.; C ispi, S. Combined An icance The apies: An O e iew o he La es Applica ions. An icance . Agen s Med. Chem. 2015,15, 408–422. [C ossRe ] 11. Vacca o, L. G een Chemis y. Beils ein J. O g. Chem. 2016,12, 2763–2765. [C ossRe ] 12. B i annica G een Chemis y. A ailable online: h ps://www.b i annica.com/science/g een-chemis y (accessed on 19 May 2020). 13. Tschan, M.J.L.; B ulé, E.; Haque e, P.; Thomas, C.M. Syn hesis o Biodeg adable Polyme s om Renewable Resou ces. Polym. Chem. 2012,3, 836–851. [C ossRe ] 14. Belgacem, M.; Gandini, A. Monome s, Polyme s and Composi es om Renewable Resou ces; Else ie : Ams e dam, The Ne he lands, 2008; ISBN 9780080453163. 15. Meie , M.A.R.; Me zge , J.O.; Schube , U.S. Plan Oil Renewable Resou ces as G een Al e na i es in Polyme Science. Chem. Soc. Re . 2007,36, 1788–1802. [C ossRe ] [PubMed] 16. Bie mann, U.; Bo nscheue , U.; Meie , M.A.R.; Me zge , J.O.; Schä e , H.J. Oils and Fa s as Renewable Raw Ma e ials in Chemis y. Angew. Chemie In . Ed. 2011,50, 3854–3871. [C ossRe ] 17. Miao, S.; Wang, P.; Su, Z.; Zhang, S. Vege able-Oil-Based Polyme s as Fu u e Polyme ic Bioma e ials. Ac a Bioma e . 2014 ,10, 1692–1704. [C ossRe ] 18. Tü ünç, O.; Meie , M.A.R. Fa y Acid De i ed Monome s and Rela ed Polyme s ia Thiol-Ene (Click) Addi ions. Mac omol. Rapid Commun. 2010,31, 1822–1826. [C ossRe ] [PubMed] 19. Del Rio, E.; Lligadas, G.; Ronda, J.C.; Galià, M.; Meie , M.A.R.; Cádiz, V. Polyu e hanes om Polyols Ob ained by ADMET Polyme iza ion o a Cas o Oil-Based Diene: Cha ac e iza ion and Shape Memo y P ope ies. J. Polym. Sci. Pa A Polym. Chem. 2011,49, 518–525. [C ossRe ] 20. Mu lu, H.; Meie , M.A.R. Cas o Oil as a Renewable Resou ce o he Chemical Indus y. Eu . J. Lipid Sci. Technol. 2010 ,112, 10–30. [C ossRe ] 21. Fi daus, M.; Meie , M.A.R.; Bie mann, U.; Me zge , J.O. Renewable Co-Polyme s De i ed om Cas o Oil and Limonene. Eu . J. Lipid Sci. Technol. 2014,116, 31–36. [C ossRe ] 22. K eye, O.; Tó h, T.; Meie , M.A.R. Poly- α , β -Unsa u a ed Aldehydes De i ed om Cas o Oil ia ADMET Polyme iza ion. Eu . J. Lipid Sci. Technol. 2011,113, 31–38. [C ossRe ] 23. Mensah, M.B.; Awudza, J.A.M.; O’B ien, P. Cas o Oil: A Sui able G een Sou ce o Capping Agen o Nanopa icle Syn heses and Facile Su ace Func ionaliza ion. R. Soc. Open Sci. 2018,5, 180824. [C ossRe ] 24. Rajalakshmi, P.; Ma ie, J.M.; Ma ia Xa ie , A.J. Cas o Oil-De i ed Monome Ricinoleic Acid Based Biodeg adable Unsa u a ed Polyes e s. Polym. Deg ad. S ab. 2019,170, 109016. [C ossRe ] 25. Lau en ino, L.S.; Medei os, A.M.M.S.; Machado, F.; Cos a, C.; A aújo, P.H.H.; Saye , C. Syn hesis o a Biobased Monome De i ed om Cas o Oil and Copolyme iza ion in Aqueous Medium. Chem. Eng. Res. Des. 2018,137, 213–220. [C ossRe ] 26. Ca doso, P.B.; Machado, T.O.; Feuse , P.E.; Saye , C.; Meie , M.A.R.; A aújo, P.H.H. Biocompa ible Polyme ic Nanopa icles F om Cas o Oil De i a i es ia Thiol-Ene Miniemulsion Polyme iza ion. Eu . J. Lipid Sci. Technol. 2018,120, 1700212. [C ossRe ] 27. Machado, T.O.; Ca doso, P.B.; Feuse , P.E.; Saye , C.; A aújo, P.H.H. Thiol-Ene Miniemulsion Polyme iza ion o a Biobased Monome o Biomedical Applica ions. Colloids Su . B Bioin e aces 2017,159, 509–517. [C ossRe ] 28. El-Say, K.M.; El-Sawy, H.S. Polyme ic Nanopa icles: P omising Pla o m o D ug Deli e y. In . J. Pha m. 2017 ,528, 675–691. [C ossRe ] 29. Chauhan, N.; Chawla, S.; Pundi , C.S.; Jain, U. An Elec ochemical Senso o De ec ion o Neu o ansmi e -Ace ylcholine Using Me al Nanopa icles, 2D Ma e ial and Conduc ing Polyme Modi ied Elec ode. Biosens. Bioelec on. 2017 ,89, 377–383. [C ossRe ] 30. Zhang, J.; Chen, H.; Zhou, T.; Wang, L.; Gao, D.; Zhang, X.; Liu, Y.; Wu, C.; Yuan, Z. A PIID-DTBT Based Semi-Conduc ing Polyme Do s wi h B oad and S ong Op ical Abso p ion in he Visible-Ligh Region: Highly E ec i e Con as Agen s o Mul iscale and Mul i-Spec al Pho oacous ic Imaging. Nano Res. 2017,10, 64–76. [C ossRe ] 31. Klepac, D.; Kos ko á, H.; Pe o a, S.; Chy il, P.; E ych, T.; Ke eïche, S.; Raška, I.; Wei z, D.A.; Filippo , S.K. In e ac ion o Spin-Labeled HPMA-Based Nanopa icles wi h Human Blood Plasma P o eins- he In oduc ion o P o ein-Co ona-F ee Polyme Nanomedicine. Nanoscale 2018,10, 6194–6204. [C ossRe ] 32. Taliano , P.; Fa khu dino a, L.I.; Timin, A.S.; Milichko, V.A.; Zyuzin, M.V. Adap i e Nanopa icle-Polyme Complexes as Op ical Elemen s: Design and Applica ion in Nanopho onics and Nanomedicine. Lase Pho onics Re . 2021,15, 2000421. [C ossRe ] 33. Khan, M.M.; Madni, A.; Filipczak, N.; Pan, J.; Rehman, M.; Rai, N.; A ia, S.A.; To chilin, V.P. Fola e Ta ge ed Lipid Chi osan Hyb id Nanopa icles o Enhanced An i-Tumo E icacy. Nanomed. Nano echnol. Biol. Med. 2020 ,28, 102228. [C ossRe ] [PubMed] 34. Naga a ma, B.V.N.; Yada , H.K.S.; Ayaz, A.; Vasudha, L.S.; Shi akuma , H.G. Di e en Techniques o P epa a ion o Polyme ic Nanopa icles—A Re iew. Asian J. Pha m. Clin. Res. 2012,5, 16–23. Pha maceu ics 2023,15, 1908 17 o 22 35. dos San os, P.C.M.; Feuse , P.E.; Ca doso, P.B.; S eine , B.T.; da Có neo, E.S.; Scussel, R.; da Viegas, A.C.; Machado-de-Á ila, R.A.; Saye , C.; de A aújo, P.H.H. E alua ion o in Vi o Cy o oxici y o Supe pa amagne ic Poly(Thioe he -Es e ) Nanopa icles on E y h ocy es, Non-Tumo (NIH3T3), Tumo (HeLa) Cells and Hype he mia S udies. J. Bioma e . Sci. Polym. Ed. 2019 ,29, 1935–1948. [C ossRe ] 36. Zhang, Z.; G ijpma, D.W.; Feijen, J. Poly(T ime hylene Ca bona e) and Monome hoxy Poly(E hylene Glycol)-Block- Poly(T ime hylene Ca bona e) Nanopa icles o he Con olled Release o Dexame hasone. J. Con ol. Release 2006 ,111, 263–270. [C ossRe ] 37. Sheikh, F.A.; Ba aka , N.A.M.; Kanjwal, M.A.; A yal, S.; Khil, M.S.; Kim, H.Y. No el Sel -Assembled Amphiphilic Poly( ε - Cap olac one)-G a ed- Poly(Vinyl Alcohol) Nanopa icles: Hyd ophobic and Hyd ophilic D ugs Ca ie Nanopa icles. J. Ma e . Sci. Ma e . Med. 2009,20, 821–831. [C ossRe ] 38. Mishima, K. Biodeg adable Pa icle Fo ma ion o D ug and Gene Deli e y Using Supe c i ical Fluid and Dense Gas. Ad . D ug Deli . Re . 2008,60, 411–432. [C ossRe ] 39. Gu ny, R.; Peppas, N.A.; Ha ing on, D.D.; Banke , G.S. De elopmen o Biodeg adable and Injec able La ices o Con olled Release o Po en D ugs. D ug De . Ind. Pha m. 1981,7, 1–25. [C ossRe ] 40. Ahlin G abna , P.; K is l, J. The Manu ac u ing Techniques o D ug-Loaded Polyme ic Nanopa icles om P e o med Polyme s. J. Mic oencapsul. 2011,28, 323–335. [C ossRe ] [PubMed] 41. Masood, F. Polyme ic Nanopa icles o Ta ge ed D ug Deli e y Sys em o Cance The apy. Ma e . Sci. Eng. C 2016 ,60, 569–578. [C ossRe ] [PubMed] 42. Quin ana -Gue e o, D.; Allémann, E.; Fessi, H.; Doelke , E. P epa a ion Techniques and Mechanisms o Fo ma ion o Biodeg ad- able Nanopa icles om P e o med Polyme s. D ug De . Ind. Pha m. 1998,24, 1113–1128. [C ossRe ] 43. Baghe zadeh-Khajehma jan, E.; Nikniazi, A.; Olyaee a , B.; Ahmadi-kandjani, S.; Nunzi, J.-M. Mo phology Enhancemen o Sel -Assembled CH3NH3PbI3 Nanopa icles h ough Cus omized Sol en E apo a ion Tempe a u es. J. C ys . G ow h 2023 ,601, 126970. [C ossRe ] 44. Ma, W.; Lopez, G.; Amedu i, B.; Takaha a, A. Fluo opolyme Nanopa icles P epa ed Using T i luo op opene Telome Based Fluo osu ac an s. Langmui 2020,36, 1754–1760. [C ossRe ] [PubMed] 45. Niyom, Y.; C espy, D.; Flood, A.E. Compa ibili y be ween D ugs and Polyme in Nanopa icles P oduced by he Miniemulsion- Sol en E apo a ion Technique. Mac omol. Ma e . Eng. 2021,306, 2100102. [C ossRe ] 46. An onie i, M.; Land es e , K. Poly eac ions in Miniemulsions. P og. Polym. Sci. 2002,27, 689–757. [C ossRe ] 47. McClemen s, D.J. Nanoemulsions e sus Mic oemulsions: Te minology, Di e ences, and Simila i ies. So Ma e 2012 ,8, 1719–1729. [C ossRe ] 48. Ugels ad, J.; El-Aasse , M.S.; Vande ho , J. Emulsion Polyme iza-Tion: Ini ia ion o Polyme iza ion in Monome D ople s. J. Polym. Sci. Polym. Le . Ed. 1973,11, 503–2013. [C ossRe ] 49. Asua, J.M. Miniemulsion Polyme isa ion. P og. Polym. Sci 2002,27, 1283–1346. [C ossRe ] 50. Fonseca, L.B.; Nele, M.; Volpa o, N.M.; Seicei a, R.C.; Pin o, J.C. P oduc ion o PMMA Nanopa icles Loaded wi h P aziquan el Th ough “In Si u” Miniemulsion Polyme iza ion. Mac omol. Reac . Eng. 2013,7, 54–63. [C ossRe ] 51. Land es e , K. Syn hesis o Colloidal Pa icles in Miniemulsions. Annu. Re . Ma e . Res. 2006,36, 231–279. [C ossRe ] 52. Scho k, F.J.; Poehlein, G.W.; Wang, S.; Reime s, J.; Rod igues, J.; Same , C. Miniemulsion Polyme iza ion. Colloids Su . A Physicochem. Eng. Asp. 1999,153, 39–45. [C ossRe ] 53. Machado, T.O.; Saye , C.; A aujo, P.H.H. Thiol-Ene Polyme isa ion: A P omising Technique o Ob ain No el Bioma e ials. Eu . Polym. J. 2017,86, 200–215. [C ossRe ] 54. Tü ünç, O.; Meie , M.A.R. A No el Polyme iza ion App oach ia Thiol-Yne Addi ion. J. Polym. Sci. Pa A Polym. Chem. 2012 ,50, 1689–1695. [C ossRe ] 55. Lowe, A.B. Thiol-Ene “Click” Reac ions and Recen Applica ions in Polyme and Ma e ials Syn hesis. Polym. Chem. 2010 ,1, 17–36. [C ossRe ] 56. Lluch, C.; Ronda, J.C.; Galiá, M.; Lligadas, G.; Cádiz, V. Rapid App oach o Biobased Telechelics h ough Two One-Po Thiol-Ene Click Reac ions. Biomac omolecules 2010,11, 1646–1653. [C ossRe ] 57. Hu, Y.; Deng, M.; Yang, H.; Chen, L.; Xiao, C.; Zhuang, X.; Chen, X. Mul i-Responsi e Co e-C osslinked Poly (Thiole he Es e ) Micelles o Sma D ug Deli e y. Polyme 2017,110, 235–241. [C ossRe ] 58. Chen, C.K.; Law, W.C.; Aalinkeel, R.; Yu, Y.; Nai , B.; Wu, J.; Mahajan, S.; Reynolds, J.L.; Li, Y.; Lai, C.K.; e al. Biodeg adable Ca ionic Polyme ic Nanocapsules o O e coming Mul id ug Resis ance and Enabling D ug-Gene Co-Deli e y o Cance Cells. Nanoscale 2014,6, 1567–1572. [C ossRe ] 59. Hoyle, C.E.; Bowman, C.N. Thiol-Ene Click Chemis y. Angew. Chem.—In . Ed. 2010,49, 1540–1573. [C ossRe ] 60. Vandenbe gh, J.; Pee e s, M.; K e schme , T.; Wagne , P.; Junke s, T. C oss-Linked Deg adable Poly( β -Thioes e ) Ne wo ks ia Amine-Ca alyzed Thiol-Ene Click Polyme iza ion. Polyme 2014,55, 3525–3532. [C ossRe ] 61. Vandenbe gh, J.; Ranie i, K.; Junke s, T. Syn hesis o (Bio)-Deg adable Poly( β -Thioes e )s ia Amine Ca alyzed Thiol-Ene Click Polyme iza ion. Mac omol. Chem. Phys. 2012,213, 2611–2617. [C ossRe ] 62. Vi ek, R.; Thangam, R.; Nipunbabu, V.; Rejee h, C.; Si asub amanian, S.; Gunaseka an, P.; Mu huchelian, K.; Kannan, S. Mul i unc ional HER2-An ibody Conjuga ed Polyme ic Nanoca ie -Based D ug Deli e y Sys em o Mul i-D ug-Resis an B eas Cance The apy. ACS Appl. Ma e . In e aces 2014,6, 6469–6480. [C ossRe ] [PubMed] Pha maceu ics 2023,15, 1908 18 o 22 63. Masood, F.; Chen, P.; Yasin, T.; Fa ima, N.; Hasan, F.; Hameed, A. Encapsula ion o Ellip icine in Poly-(3-Hyd oxybu y a e- Co-3-Hyd oxy ale a e) Based Nanopa icles and I s in Vi o Applica ion. Ma e . Sci. Eng. 2013 ,33, 1054–1106. [C ossRe ] [PubMed] 64. Masood, F.; Chen, P.; Yasin, T.; Hasan, F.; Ahmad, B.; Hameed, A. Syn hesis o Poly-(3-Hyd oxybu y a e-Co-12 Mol % 3- Hyd oxy ale a e) by Bacillus Ce eus FB11: I s Cha ac e iza ion and Applica ion as a D ug Ca ie . J. Ma e . Sci. Ma e . Med. 2013 , 24, 1927–1937. [C ossRe ] 65. Shah, M.; Ullah, N.; Choi, M.H.; Kim, M.O.; Yoon, S.C. Amo phous Amphiphilic P(3HV-Co-4HB)-b-MPEG Block Copolyme Syn hesized om Bac e ial Copolyes e ia Mel T anses e i ica ion: Nanopa icle P epa a ion, Cispla in-Loading o Cance The apy and in Vi o E alua ion. Eu . J. Pha m. Biopha m. 2012,80, 518–527. [C ossRe ] [PubMed] 66. Shah, M.; Im an, M.; Hwan, M.; Ok, M.; Chul, S. Amphiphilic PHA—MPEG Copolyme ic Nanocon aine s o D ug Deli e y: P epa a ion, Cha ac e iza ion and in Vi o E alua ion. In . J. Pha m. 2010,400, 165–175. [C ossRe ] 67. Vilos, C.; Mo ales, F.A.; Sola , P.A.; He e a, N.S.; Gonzalez-Nilo, F.D.; Aguayo, D.A.; Mendoza, H.L.; Come , J.; B a o, M.L.; Gonzalez, P.A.; e al. Pacli axel-PHBV Nanopa icles and Thei Toxici y o Endome ial and P ima y O a ian Cance Cells. Bioma e ials 2013,34, 4098–4108. [C ossRe ] 68. Lu, X.Y.; Zhang, Y.; Wang, L. P epa a ion and in Vi o D ug-Release Beha io o 5-Fluo ou acil-Loaded Poly(Hyd oxybu y a eco- Hyd oxyhexanoa e) Nanopa icles and Mic opa icles. J. Appl. Polym. Sci. 2010,116, 2944–2950. 69. Kılıçay, E.; Demi bilek, M.; Tü k, M.; Gü en, E.; Haze , B.; Denkbas, E.B. P epa a ion and Cha ac e iza ion o Poly(3- Hyd oxybu y a e-Co-3-Hyd oxyhexanoa e) (PHBHHX) Based Nanopa icles o Ta ge ed Cance The apy. Eu . J. Pha m. Sci. 2011,44, 310–320. [C ossRe ] 70. Chan, Z.; Zhao, L.; Dong, Y.; Zhang, X.; Lin, J.; Chen, Z. Fola e-Media ed Poly(3-Hyd oxybu y a e-Co-3-Hyd oxyoc anoa e) Nanopa icles o Ta ge ing D ug Deli e y. Eu . J. Pha m. Biopha m. 2010,76, 10–16. 71. Yao, Y.-C.; Zhan, X.-Y.; Zhang, J.; Zou, X.-H.; Wang, Z.-H.; Xiong, Y.-C.; Chen, J.; Chen, G.-Q. A Speci ic D ug Ta ge ing Sys em Based on Polyhyd oxyalkanoa e G anule Binding P o ein PhaP Fused wi h Ta ge ed Cell Ligands. Bioma e ials 2008 ,29, 4823–4830. [C ossRe ] [PubMed] 72. Va an, C.; Bilensoy, E. De elopmen o Implan able Hyd oxyp opyl- β -Cyclodex in Coa ed Polycap olac one Nanopa icles o he Con olled Deli e y o Doce axel o Solid Tumo s. J. Incl. Phenom. Mac ocycl. Chem. 2014,80, 9–15. [C ossRe ] 73. Ci panli, Y.; Bilensoy, E.; Do˘gan, A.L.; Cali¸s, S. Compa a i e E alua ion o Polyme ic and Amphiphilic Cyclodex in Nanopa icles o E ec i e Camp o hecin Deli e y. Eu . J. Pha m. Biopha m. 2009,73, 82–89. [C ossRe ] [PubMed] 74. Pe e , F.; Du ou , M.; Che alie , Y.; Pa o -Lopez, H. Design, Syn hesis, and In Vi o E alua ion o New Amphiphilic Cyclodex in-Based Nanopa icles o he Inco po a ion and Con olled Release o Acyclo i . Eu . J. Pha m. Biopha m. 2013 ,83, 25–32. [C ossRe ] [PubMed] 75. Miao, Q.; Li, S.; Han, S.; Wang, Z.; Wu, Y.; Nie, G. Cons uc ion o Hyd oxyp opyl- β -Cyclodex in Copolyme Nanopa icles and Ta ge ing Deli e y o Pacli axel. J. Nanopa icle Res. 2012,14, 1043. [C ossRe ] 76. F ei e, N.F.; Feuse , P.E.; da Sil a Abel, J.; Machado-de-Á ila, R.A.; Lopes Fialho, R.; Cab al Albuque que, E.; Saye , C.; He mes de A aújo, P.H. Zinc Ph halocyanine Encapsula ion ia Thiol-Ene Miniemulsion Polyme iza ion and in Vi o Pho oxici y S udies. In . J. Polym. Ma e . Polym. Bioma e . 2020,71, 349–358. [C ossRe ] 77. F ei e, N.; Emílio, P.; Ma ia, E.; Ambel, T.; Co dani, M.; Zielinski, A.F.; Saye , C.; De Pie i, E.; A ila, R.A.M.; Hen ique, P.; e al. Colloids and Su aces A: Physicochemical and Enginee ing Aspec s P epa a ion and Cha ac e iza ion o Full-Spec um Cannabis Ex ac Loaded Poly ( Thioe he -Es e ) Nanopa icles: In Vi o E alua ion o Thei An i umo al E icacy. Colloids Su . A Physicochem. Eng. Asp. 2023,658, 130676. [C ossRe ] 78. Feuse , P.E.; dos San os, P.C.M.; Co dei o, A.P.; S e anes, N.M.; Wal e , L.O.; Maio al, M.F.; San os-Sil a, M.C.; de A aújo, P.H.H.; Saye , C. An ineoplas ic Ac i i y o F ee 4-Ni ochalcone and Encapsula ed in Poly(Thioe he -Es e ) Nanopa icles Ob ained by Thiol-Ene Polyme iza ion in Two Human Leukemia Cell Lines (Ju ka and K562). J. D ug Deli . Sci. Technol. 2022 ,67, 102924. [C ossRe ] 79. Danhie , F.; Lecou u ie , N.; V oman, B.; Je ome, C.; Ma chand-B ynae , J.; Fe on, O.; P éa , V. Pacli axel-Loaded PEGyla ed PLGA-Based Nanopa icles: In Vi o and in Vi o E alua ion. J. Con ol. Release 2009,133, 11–17. [C ossRe ] 80. Khu oo, T.; Ve ma, D.; Talegaonka , S.; Padhi, S.; Panda, A.K.; Iqbal, Z. Topo ecan–Tamoxi en Duple PLGA Polyme ic Nanopa i- cles: In es iga ion o in Vi o, in Vi o and Cellula Up ake Po en ial. In . J. Pha m. 2014,473, 384–394. [C ossRe ] 81. Chái ez-Ramí ez, M.; Sánchez-Bu gos, J.; Gomes, C.; Mo eno-Jiménez, M.; González-La edo, R.; Be nad-Be nad, M.; Medina- To es, L.; Ramí ez-Ma es, M.; Gallegos-In an e, J.; Rocha-Guzmán, N. Mo phological and Release Cha ac e iza ion o Nanopa i- cles Fo mula ed wi h Poly (Dl-Lac ide-Co-Glycolide) (PLGA) and Lupeol: In Vi o Pe meabili y and Modula o E ec on NF-KB in Caco-2 Cell Sys em S imula ed wi h TNF-α.Food Chem. Toxicol. 2015,85, 2–9. [C ossRe ] 82. Jaide , L.R.; K ishnan, U.M.; Se hu aman, S. Gemci abine Loaded Biodeg adable PLGA Nanosphe es o in Vi o Panc ea ic Cance The apy. Ma e . Sci. Eng. C. Ma e . Biol. Appl. 2015,47, 40–47. [C ossRe ] 83. De akhshandeh, K.; E an, M.; Dadashzadeh, S. Encapsula ion o 9-Ni ocamp o hecin, a No el An icance D ug, in Biodeg adable Nanopa icles: Fac o ial Design, Cha ac e iza ion and Release Kine ics. Eu . J. Pha m. Biopha m. 2007,66, 34–41. [C ossRe ] 84. Wang, H.; Zhao, Y.; Wu, Y.; Hu, Y.-L.; Nan, K.; Nie, G.; Chen, H. Enhanced An i-Tumo E icacy by Co-Deli e y o Doxo ubicin and Pacli axel wi h Amphiphilic Me hoxy PEG-PLGA Copolyme Nanopa icles. Bioma e ials 2011,32, 8281–8290. [C ossRe ] Pha maceu ics 2023,15, 1908 19 o 22 85. Le B oc-Ryckewae , D.; Ca pen ie , R.; Lipka, E.; Dahe , S.; Vacche , C.; Be bede , D.; Fu man, C. De elopmen o Inno a i e Pacli axel-Loaded Small PLGA Nanopa icles: S udy o Thei An ip oli e a i e Ac i i y and Thei Molecula In e ac ions on P os a ic Cance Cells. In . J. Pha m. 2013,454, 712–719. [C ossRe ] [PubMed] 86. Ma heolabakis, G.; Taou ik, E.; Ha alambous, S.; Robe s, M.L.; A gous akis, K. In Vi o In es iga ion o Tole ance and An i umo Ac i i y o Cispla in-Loaded PLGA-MPEG Nanopa icles. Eu . J. Pha m. Biopha m. 2009,71, 190–195. [C ossRe ] [PubMed] 87. Schleich, N.; Sib e , P.; Danhie , P.; Ucaka , B.; Lau en , S.; Mulle ; Jé ôme, C.; Gallez, B.; P éa , V.; Danhie , F. Dual An icance D ug/Supe pa amagne ic I on Oxide-Loaded PLGAbased Nanopa icles o Cance The apy and Magne ic Resonance Imaging. In . J. Pha m. 2013,447, 94–101. [C ossRe ] [PubMed] 88. Jain, A.K.; Thanki, K.; Jain, S. Co-Encapsula ion o Tamoxi en and Que ce in in Polyme ic Nanopa icles: Implica ions on O al Bioa ailabili y, An i umo E icacy, and D ug-Induced Toxici y. Mol. Pha m. 2013,10, 3459–3474. [C ossRe ] 89. Chan, J.M.; Zhang, L.; Yue , K.P.; Liao, G.; Rhee, J.W.; Lange , R.; Fa okhzad, O.C. PLGA-Leci hin-PEG Co e-Shell Nanopa icles o Con olled D ug Deli e y. Bioma e ials 2009,30, 1627–1634. [C ossRe ] 90. Ma ín-Bande as, L.; Muñoz-Rubio, I.; P ados, J.; Ál a ez-Fuen es, J.; Calde ón-Mon año, J.M.; López-Láza o, M.; A ias, J.L.; Lei a, M.C.; Holgado, M.A.; Fe nández-A é alo, M. In Vi o and In Vi o E alua ion o Del a9-Te ahid ocannabinol/PLGA Nanopa icles o Cance Chemo he apy. In . J. Pha m. 2015,487, 205–212. [C ossRe ] 91. Chi asupho, C.; Xie, S.-X.; Baoum, A.; Yako le a, T.; Siahaan, T.J.; Be kland, C.J. ICAM-1 Ta ge ing o Doxo ubicin-Loaded PLGA Nanopa icles o Lung Epi helial Cells. Eu . J. Pha m. Sci. 2009,37, 141–150. [C ossRe ] 92. Liang, C.; Yang, Y.; Ling, Y.; Huang, Y.; Li, T.; Li, X. Imp o ed The apeu ic E ec o Fola e-Deco a ed PLGA-PEG Nanopa icles o Endome ial Ca cinoma. Bioo ganic Med. Chem. 2011,19, 4057–4066. [C ossRe ] 93. Dhas, N.L.; Ige, P.P.; Kuda ha, R.R. Design, Op imiza ion and in-Vi o S udy o Folic Acid Conjuga ed-Chi osan Func ionalized PLGA Nanopa icle o Deli e y o Bicalu amide in P os a e Cance . Powde Technol. 2015,283, 234–245. [C ossRe ] 94. Su, W.-C.; Su, W.-P.; Cheng, F.-Y.; Shieh, D.-B.; Yeh, C.-S. PLGA Nanopa icles Codeli e Pacli axel and S a 3 SiRNA o O e come Cellula Resis ance in Lung Cance Cells. In . J. Nanomed. 2012,7, 4269–4283. [C ossRe ] 95. Cui, Y.; Xu, Q.; Chow, P.K.-H.; Wang, D.; Wang, C.-H. T ans e in-Conjuga ed Magne ic Silica PLGA Nanopa icles Loaded wi h Doxo ubicin and Pacli axel o B ain Glioma T ea men . Bioma e ials 2013,34, 8511–8520. [C ossRe ] [PubMed] 96. Jain, A.; Jain, A.; Ga g, N.K.; Tyagi, R.K.; Singh, B.; Ka a e, O.P.; Webs e , T.J.; Soni, V. Su ace Enginee ed Polyme ic Nanoca ie s Media e he Deli e y o T ans e in-Me ho exa e Conjuga es o an Imp o ed Unde s anding o B ain Cance . Ac a Bioma e . 2015,24, 140–151. [C ossRe ] [PubMed] 97. Dha , S.; Gu, F.X.; Lange , R.; Fa okhzad, O.C.; Lippa d, S.J. Ta ge ed Deli e y o Cispla in o P os a e Cance Cells by Ap ame Func ionalized P (IV) P od ug-PLGA-PEG Nanopa icles. P oc. Na l. Acad. Sci. USA 2008 ,105, 7356–17361. [C ossRe ] [PubMed] 98. Chi asupho, C.; Li dp apamongkol, K.; Kewsuwan, P.; Sa isu a, N. Ta ge ed Deli e y o Doxo ubicin o A549 Lung Cance Cells by CXCR4 An agonis Conjuga ed PLGA Nanopa icles. Eu . J. Pha m. Biopha m. 2014,88, 529–538. [C ossRe ] 99. Danhie , F.; Pou celle, V.; Ma chand-B ynae , J.; Jé ôme, C.; Fe on, O.; P éa , V. Ta ge ing o Tumo Endo helium by RGD-G a ed PLGA-Nanopa icles. Me hods Enzym. 2012,508, 157–175. 100. Li, L.; Xiang, D.; Shigda , S.; Yang, W.; Li, Q.; Lin, J.; Liu, K.; Duan, W. Epi helial Cell Adhesion Molecule Ap ame Func ionalized PLGA-Leci hincu cumin-PEG Nanopa icles o Ta ge ed D ug Deli e y o Human Colo ec al Adenoca cinoma Cells. In . J. Nanomed. 2014,9, 1083–1096. 101. Chen, H.; Gao, J.; Lu, Y.; Kou, G.; Zhang, H.; Fan, L.; Sun, Z.; Guo, Y.; Zhong, Y. P epa a ion and Cha ac e iza ion o PE38KDEL- Loaded An i-HER2 Nanopa icles o Ta ge ed Cance The apy. J. Con ol. Release 2008,128, 209–216. [C ossRe ] 102. A a ind, A.; Nai , R.; Ra eend an, S.; Vee ana ayanan, S.; Nagaoka, Y.; Fukuda, T.; Hasumu a, T.; Mo imo o, H.; Yoshida, Y.; Maekawa, T.; e al. Ap ame Conjuga ed Pacli axel and Magne ic Fluid Loaded Fluo escen ly Tagged PLGA Nanopa icles o Ta ge ed Cance The apy. J. Magn. Magn. Ma e . 2013,344, 116–123. [C ossRe ] 103. Agga wal, S.; Yada , S.; Gup a, S. EGFR Ta ge ed PLGA Nanopa icles Using Gemci abine o T ea men o Panc ea ic Cance . J. Biomed. Nano echnol. 2011,7, 137–138. [C ossRe ] 104. Na ayanan, S.; Mony, U.; Vijaykuma , D.K.; Koyaku y, M.; Paul-P asan h, B.; Menon, D. Sequen ial Release o Epigalloca echin Galla e and Pacli axel om PLGA-Casein Co e/Shell Nanopa icles Sensi izes D ug-Resis an B eas Cance Cells. Nanomed. Nano echnol. Biol. Med. 2015,11, 1399–1406. [C ossRe ] [PubMed] 105. Wei, K.; Peng, X.; Zou, F. Fola e-Deco a ed PEG-PLGA Nanopa icles wi h Silica Shells o Capeci abine Con olled and Ta ge ed Deli e y. In . J. Pha m. 2014,464, 225–233. [C ossRe ] [PubMed] 106. Vanga a, K.K.; Liu, J.L.; Palaku hi, S. Hyalu onic Acid-Deco a ed PLGAPEG Nanopa icles o Ta ge ed Deli e y o SN-38 o O a ian Cance . An icance Res. 2013,33, 2425–2434. [PubMed] 107. Kocbek, P.; Obe maje , N.; Cegna , M.; Kos, J.; K is l, J. Ta ge ing Cance Cells Using PLGA Nanopa icles Su ace Modi ied wi h Monoclonal An ibody. J. Con ol. Release 2007,120, 18–26. [C ossRe ] [PubMed] 108. Bha iya, P.; Chawla, R.; Du a, P.K. PH-Responsi e Cha ge-Con e ible N-Succinyl Chi osan-Que ce in Coo dina ion Polyme Nanopa icles o E ec i e NIR Pho o he mal Cance The apy. Mac omol. Chem. Phys. 2022,223, 2200140. [C ossRe ] 109. Gogoi, P.; Du a, A.; Ram eke, A.; Maji, T.K. P epa a ion, Cha ac e iza ion and Cy o oxic Applica ions o Cu cumin-( ± ) α -Lipoic Acid Coloaded Phospho yla ed Chi osan Nanopa icles in MDA MB 231 B eas Cance Cell Line. Polym. Ad . Technol. 2020 ,31, 2827–2841. [C ossRe ] Pha maceu ics 2023,15, 1908 20 o 22 110. Snima, K.S.; Jayakuma , R.; Lakshmanan, V.K. In Vi o and in Vi o Biological E alua ion o O-Ca boxyme hyl Chi osan Encapsula ed Me o min Nanopa icles o Panc ea ic Cance The apy. Pha m. Res. 2014,31, 3361–3370. [C ossRe ] 111. Ding, Y.F.; Li, S.; Liang, L.; Huang, Q.; Yuwen, L.; Yang, W.; Wang, R.; Wang, L.H. Highly Biocompa ible Chlo in E6-Loaded Chi osan Nanopa icles o Imp o ed Pho odynamic Cance The apy. ACS Appl. Ma e . In e aces 2018 ,10, 9980–9987. [C ossRe ] 112. Kou, C.H.; Han, J.; Han, X.L.; Zhuang, H.J.; Zhao, Z.M. P epa a ion and Cha ac e iza ion o he Ad iamycin-Loaded Amphiphilic Chi osan Nanopa icles and Thei Applica ion in he T ea men o Li e Cance . Oncol. Le . 2017,14, 7833–7841. [C ossRe ] 113. Ma, Y.; Zheng, Y.; Zeng, X.; Jiang, L.; Chen, H.; Liu, R.; Huang, L.; Mei, L. No el Doce axel-Loaded Nanopa icles Based on PCL-Tween 80 Copolyme o Cance T ea men . In . J. Nanomed. 2011,6, 2679–2688. 114. Chen, L.X.; Ni, X.L.; Zhang, H.; Wu, M.; Liu, J.; Xu, S.; Yang, L.L.; Fu, S.Z.; Wu, J. P epa a ion, Cha ac e iza ion, in Vi o and in Vi o An i-Tumo E ec o Thalidomide Nanopa icles on Lung Cance . In . J. Nanomed. 2018 ,13, 2463–2476. [C ossRe ] [PubMed] 115. Raspan ini, G.L.; Luiz, M.T.; Ab ia a, J.P.; de Eloy, J.O.; Vaide go n, M.M.; da Eme y, F.S.; Ma che i, J.M. PCL-TPGS Polyme ic Nanopa icles o Doce axel Deli e y o P os a e Cance : De elopmen , Physicochemical and Biological Cha ac e iza ion. Colloids Su . A Physicochem. Eng. Asp. 2021,627, 127144. [C ossRe ] 116. Lu, Y.; Wen, Q.; Luo, J.; Xiong, K.; Wu, Z.X.; Wang, B.Q.; Chen, Y.; Yang, B.; Fu, S.Z. Sel -Assembled Dihyd oa emisinin Nanopa icles as a Pla o m o Ce ical Cance Chemo he apy. D ug Deli . 2020,27, 876–887. [C ossRe ] [PubMed] 117. Liu, X.; Li, J.; Huang, L.; Yang, J.; Wang, Y.; Yang, M.; Tang, M.; Qiu, T. P epa a ion and E alua ion o MPEG-PCL Polyme ic Nanopa icles Agains Gas ic Cance . J. Wuhan Uni . Technol. Ma e . Sci. Ed. 2020,35, 1162–1168. [C ossRe ] 118. Xiong, K.; Zhang, Y.; Wen, Q.; Luo, J.; Lu, Y.; Wu, Z.X.; Wang, B.Q.; Chen, Y.; Zhao, L.; Fu, S.Z. Co-Deli e y o Pacli axel and Cu cumin by Biodeg adable Polyme ic Nanopa icles o B eas Cance Chemo he apy. In . J. Pha m. 2020 ,589, 119875. [C ossRe ] 119. Rao, S.V.; Kuma , S.S. MPEG-PCL Nanopa icles as New Ca ie s o Deli e y o a P os ae Cance D ug Fluamide. Res. J. Pha m. Technol. 2021,14, 3657–3661. [C ossRe ] 120. Bad an, M.M.; Mady, M.M.; Ghannam, M.M.; Shakeel, F. P epa a ion and Cha ac e iza ion o Polyme ic Nanopa icles Su ace Modi ied wi h Chi osan o Ta ge T ea men o Colo ec al Cance . In . J. Biol. Mac omol. 2017,95, 643–649. [C ossRe ] 121. Pa el, P.; Ra al, M.; Man a , A.; Ai ao, V.; Bha , V.; Shah, P. Lung Cance Ta ge ing E iciency o Silibinin Loaded Poly Cap olac one /Plu onic F68 Inhalable Nanopa icles: In Vi o and In Vi o S udy. PLoS ONE 2022,17, e0267257. [C ossRe ] 122. Li, M.; Tang, Z.; Lin, J.; Zhang, Y.; L , S.; Song, W.; Huang, Y.; Chen, X. Syne gis ic An i umo E ec s o Doxo ubicin-Loaded Ca boxyme hyl Cellulose Nanopa icle in Combina ion wi h Endos a o E ec i e T ea men o Non-Small-Cell Lung Cance . Ad . Heal hc. Ma e . 2014,3, 1877–1888. [C ossRe ] 123. Yuse i, M.; Lee-Kiun, M.S.; Shameli, K.; Teow, S.Y.; Ali, R.R.; Siew, K.K.; Chan, H.Y.; Wong, M.M.T.; Lim, W.L.; Kuˇca, K. 5- Fluo ou acil Loaded Magne ic Cellulose Bionanocomposi es o Po en ial Colo ec al Cance T ea men . Ca bohyd . Polym. 2021 , 273, 118523. [C ossRe ] [PubMed] 124. Asabuwa Ngwabebhoh, F.; Ilka E dagi, S.; Yildiz, U. Picke ing Emulsions S abilized Nanocellulosic-Based Nanopa icles o Couma in and Cu cumin Nanoencapsula ions: In Vi o Release, An icance and An imic obial Ac i i ies. Ca bohyd . Polym. 2018 , 201, 317–328. [C ossRe ] [PubMed] 125. Han, L.; Ren, Y.; Long, L.; Zhong, Y.; Shen, C.; Pu, P.; Yuan, X.; Kang, C. Inhibi ion o C6 Glioma in Vi o by Combina ion Chemo he apy o Implan a ion o Polyme Wa e and In aca o id Pe usion o T ans e in-Deco a ed Nanopa icles. Oncol. Rep. 2012,27, 121–128. [C ossRe ] [PubMed] 126. Feuse , P.E.; Bubniak, L.D.S.; Bodack, C.D.N.; Valé io, A.; Sil a, M.C.D.S.; Ricci, E.; Saye , C.; De A aújo, P.H.H. In Vi o Cy o oxici y o Poly(Me hyl Me hac yla e) Nanopa icles and Nanocapsules Ob ained by Miniemulsion Polyme iza ion o D ug Deli e y Applica ion. J. Nanosci. Nano echnol. 2016,16, 7669–7676. [C ossRe ] 127. Guo, W.; Wang, T.; Huang, C.; Ning, S.; Guo, Q.; Zhang, W.; Yang, H.; Zhu, D.; Huang, Q.; Qian, H.; e al. Pla ele Memb ane- Coa ed C-TiO2 Hollow Nanosphe es o Combined Sonodynamic and Alkyl-Radical Cance The apy. Nano Res. 2023 ,16, 782–791. [C ossRe ] 128. Liu, D.; Dai, X.; Zhang, W.; Zhu, X.; Zha, Z.; Qian, H.; Cheng, L.; Wang, X. Liquid Ex olia ion o Ul asmall Zi conium Ca bide Nanodo s as a Nonin lamma o y Pho o he mal Agen in he T ea men o Glioma. Bioma e ials 2023,292, 121917. [C ossRe ] 129. Ning, S.; Dai, X.; Tang, W.; Guo, Q.; Lyu, M.; Zhu, D.; Zhang, W.; Qian, H.; Yao, X.; Wang, X. Cance Cell Memb ane-Coa ed C-TiO2 Hollow Nanoshells o Combined Sonodynamic and Hypoxia-Ac i a ed Chemo he apy. Ac a Bioma e . 2022 ,152, 562–574. [C ossRe ] 130. Wang, X.; Wang, X.; Yue, Q.; Xu, H.; Zhong, X.; Sun, L.; Li, G.; Gong, Y.; Yang, N.; Wang, Z.; e al. Liquid Ex olia ion o TiN Nanodo s as No el Sonosensi ize s o Pho o he mal-Enhanced Sonodynamic The apy agains Cance . Nano Today 2021 ,39, 101170. [C ossRe ] 131. Guo, Q.; Yin, M.; Fan, J.; Yang, Y.; Liu, T.; Qian, H.; Dai, X.; Wang, X. Pe oxidase-Mimicking TA-VOx Nanob anches o Enhanced Pho o he mal/Chemodynamic The apy o Glioma by Inhibi ing he Exp ession o HSP60. Ma e . Des. 2022 ,224, 111366. [C ossRe ] 132. Mon ané, X.; Bajek, A.; Roszkowski, K.; Mon o nés, J.M.; Giambe ini, M.; Roszkowski, S.; Kowalczyk, O.; Ga cia-Valls, R.; Tylkowski, B. Encapsula ion o Cance The apy. Molecules 2020,25, 1605. [C ossRe ] 133. Ki le, Z.D.; Tadele, M.; Alemu, E.; Gedamu, T.; Ayele, A.G. A Recen De elopmen o New The apeu ic Agen s and No el D ug Ta ge s o Cance T ea men . SAGE Open Med. 2021,9, 205031212110670. [C ossRe ] Pha maceu ics 2023,15, 1908 21 o 22 134. Wadhwa, K.; Kadian, V.; Pu i, V.; Bha dwaj, B.Y.; Sha ma, A.; Pahwa, R.; Rao, R.; Gup a, M.; Singh, I. New Insigh s in o Que ce in Nano o mula ions o Topical Deli e y. Phy omed. Plus 2022,2, 100257. [C ossRe ] 135. Lawson, M.K. Imp o emen o The apeu ic Value o Que ce in wi h Chi osan Nanopa icle Deli e y Sys ems and Po en ial Applica ions. In . J. Mol. Sci. 2023,24, 3293. [C ossRe ] [PubMed] 136. Kuma , D.; Gau am, A.; Kundu, P.P. Syn hesis o PH-Sensi i e G a ed Psyllium: Encapsula ion o Que ce in o Colon Cance T ea men . J. Appl. Polym. Sci. 2022,139, 51552. [C ossRe ] 137. Chen, L.C.; Chen, Y.C.; Su, C.Y.; Hong, C.S.; Ho, H.O.; Sheu, M.T. De elopmen and Cha ac e iza ion o Sel -Assembling Leci hin-Based Mixed Polyme ic Micelles Con aining Que ce in in Cance T ea men and an in Vi o Pha macokine ic S udy. In . J. Nanomed. 2016,11, 1557–1566. [C ossRe ] 138. de Redín, I.L.; Expósi o, F.; Agüe os, M.; Collan es, M.; Peñuelas, I.; Allemandi, D.; Llabo , J.M.; Cal o, A.; I ache, J.M. In Vi o E icacy o Be acizumab-Loaded Albumin Nanopa icles in he T ea men o Colo ec al Cance . D ug Deli . T ansl. Res. 2020 ,10, 635–645. [C ossRe ] [PubMed] 139. Ba aglia, L.; Galla a e, M.; Pei a, E.; Chi io, D.; Solazzi, I.; Gio dano, S.M.A.; Giglio i, C.L.; Rigan i, C.; Dianzani, C. Be acizumab Loaded Solid Lipid Nanopa icles P epa ed by he Coace a ion Technique: P elimina y in Vi o S udies. Nano echnology 2015 ,26, 255102. [C ossRe ] 140. Sousa, F.; Dhaliwal, H.K.; Ga acceca, F.; Sa men o, B.; Amiji, M.M. Enhanced An i-Angiogenic E ec s o Be acizumab in Glioblas oma T ea men upon In anasal Adminis a ion in Polyme ic Nanopa icles. J. Con ol. Release 2019 ,309, 37–47. [C ossRe ] [PubMed] 141. Di Filippo, L.D.; Dua e, J.L.; Azambuja, J.H.; Mancuso, R.I.; Luiz, M.T.; A aújo, V.H.S.; Figuei edo, I.D.; Ba e o-de-Souza, L.; Sábio, R.M.; Sasso-Ce i, E.; e al. Glioblas oma Mul i o me Ta ge ed Deli e y o Doce axel Using Be acizumab-Modi ied Nanos uc u ed Lipid Ca ie s Impai in Vi o Cell G ow h and in Vi o Tumo P og ession. In . J. Pha m. 2022 ,618, 121682. [C ossRe ] 142. Si i, Z.S.; Ahmad, N.H.; Hamid, S. Cha ac e iza ion o PLGA-PEG Ca ha an hus Roseus Nanopa icles and Assessing I s An icance E ec s in He 2-O e exp essed B eas Cance Cells. Pha macogn. Mag. 2022,18, 273. 143. Ke, Y.; Al Aboody, M.S.; Al u aiki, W.; Alsagaby, S.A.; Al aiz, F.A.; Vee a agha an, V.P.; Mickyma ay, S. Pho osyn hesized Gold Nanopa icles om Ca ha an hus Roseus Induces Caspase-Media ed Apop osis in Ce ical Cance Cells (HeLa). A i . Cells Nanomed. Bio echnol. 2019,47, 1938–1946. [C ossRe ] 144. Azha , N.A.; Ghozali, S.Z.; Baka , S.A.A.; Lim, V.; Ahmad, N.H. Supp essing G ow h, Mig a ion, and In asion o Human Hepa ocellula Ca cinoma HepG2 Cells by Ca ha an hus Roseus-sil e Nanopa icles. Toxicol. Vi . 2020 ,67, 104910. [C ossRe ] [PubMed] 145. Liu, Y.; Zhang, H.; Cui, H.; Zhang, F.; Zhao, L.; Liu, Y.; Meng, Q. Combined and Ta ge ed D ugs Deli e y Sys em o Colo ec al Cance T ea men : Cona umumab Deco a ed, Reac i e Oxygen Species Sensi i e I ino ecan P od ug and Que ce in Co-Loaded Nanos uc u ed Lipid Ca ie s. D ug Deli . 2022,29, 342–350. [C ossRe ] [PubMed] 146. Liu, X.; Jiang, J.; Chan, R.; Ji, Y.; Lu, J.; Liao, Y.P.; Okene, M.; Lin, J.; Lin, P.; Chang, C.H.; e al. Imp o ed E icacy and Reduced Toxici y Using a Cus om-Designed I ino ecan-Deli e ing Silicasome o O ho opic Colon Cance . ACS Nano 2019 ,13, 38–53. [C ossRe ] [PubMed] 147. Hong, J.; Feng, Z. Syne gic Fab ica ion o Combina ion The apy o I ino ecan and 5-Fluo ou acil Encapsula ed Polyme ic Nanopa icles o he T ea men o Gas ic Cance The apy. P ocess Biochem. 2021,106, 191–198. [C ossRe ] 148. F aguas-Sánchez, A.I.; To es-Suá ez, A.I.; Cohen, M.; Delie, F.; Bas ida-Ruiz, D.; Ya , L.; Ma in-Sab oso, C.; Fe nández- Ca ballido, A. PLGA Nanopa icles o he In ape i oneal Adminis a ion o CBD in he T ea men o O a ian Cance : In Vi o and in O o Assessmen . Pha maceu ics 2020,12, 439. [C ossRe ] [PubMed] 149. De La Ossa, D.H.P.; Gil-Aleg e, M.E.; Lig es i, A.; Abe u as, M.D.R.; Molpece es, J.; To es, A.I.; Di Ma zo, V. P epa a ion and Cha ac e iza ion o Del a9-Te ahyd ocannabinol-Loaded Biodeg adable Polyme ic Mic opa icles and Thei An i umo al E icacy on Cance Cell Lines. J. D ug Ta ge . 2013,21, 710–718. [C ossRe ] 150. Tangu oo i, S.; Ko ideck, H.; Mak igio gos, M.; Co mack, R.; S idha , S. A No el Nano-Fo mula ion o Sys emic Adminis a ion o PARPi-Olapa ib (Nano-Olapa ib) o Radiosensi iza ion, Chemosensi iza ion, and Combina o ial The apy in P os a e Cance . Mol. Cance The . 2013,12, A81. [C ossRe ] 151. Zhang, S.; Li, E.; Liu, Z.; Shang, H.; Chen, Y.; Jing, H. Anopa icle-Based Olapa ib Deli e y Enhances I s E ec , and Imp o es D ug Sensi i i y o Cispla in in T iple Nega i e B eas Cance . J. D ug Deli . Sci. Technol. 2022,76, 103731. [C ossRe ] 152. Anwe , M.K.; Ali, E.A.; Iqbal, M.; Ahmed, M.M.; Aldawsa i, M.F.; Al Saq , A.; Alalaiwe, A.; Soliman, G.A. De elopmen o Chi osan-Coa ed PLGA-Based Nanopa icles o Imp o ed O al Olapa ib Deli e y: In Vi o Cha ac e iza ion, and In Vi o Pha macokine ic S udies. P ocesses 2022,10, 1329. [C ossRe ] 153. Jeya aj, M.; Rajesh, M.; A un, R.; Muba akAli, D.; Sa hishkuma , G.; Si anandhan, G.; De , G.K.; Manicka asagam, M.; P emkuma , K.; Thajuddin, N.; e al. An In es iga ion on he Cy o oxici y and Caspase-Media ed Apop o ic E ec o Biologically Syn hesized Sil e Nanopa icles Using Podophyllum Hexand um on Human Ce ical Ca cinoma Cells. Colloids Su . B Bioin e aces 2013,102, 708–717. [C ossRe ] 154. Kumbha , P.S.; Saka e, A.M.; Pa il, O.B.; Manjappa, A.S.; Disouza, J.I. Podophyllo oxin-Polyac ylic Acid Conjuga e Micelles: Imp o ed An icance E icacy agains Mul id ug-Resis an B eas Cance . J. Egyp . Na l. Canc. Ins . 2020 ,32, 42. [C ossRe ] [PubMed] Pha maceu ics 2023,15, 1908 22 o 22 155. Li, Y.; Chen, M.; Yao, B.; Lu, X.; Zhang, X.; He, P.; Vasila os, S.N.; Ren, X.; Bian, W.; Yao, C. T ans e in Recep o -Ta ge ed Redox/PH-Sensi i e Podophyllo oxin P od ug Micelles o Mul id ug-Resis an B eas Cance The apy. J. Ma e . Chem. B 2019 ,7, 5814–5824. [C ossRe ] 156. Zhang, P.; Tang, M.; Huang, Q.; Zhao, G.; Huang, N.; Zhang, X.; Tan, Y.; Cheng, Y. Combina ion o 3-Me hyladenine The apy and Asn-Gly-A g (NGR)-Modi ied Mesopo ous Silica Nanopa icles Loaded wi h Temozolomide o Glioma The apy in Vi o. Biochem. Biophys. Res. Commun. 2019,509, 549–556. [C ossRe ] [PubMed] 157. Fang, C.; Wang, K.; S ephen, Z.R.; Mu, Q.; Kie i , F.M.; Chiu, D.T.; P ess, O.W.; Zhang, M. Temozolomide Nanopa icles o Ta ge ed Glioblas oma The apy. ACS Appl. Ma e . In e aces 2015,7, 6674–6682. [C ossRe ] 158. Li, K.; Liang, N.; Yang, H.; Liu, H.; Li, S. Temozolomide Encapsula ed and Folic Acid Deco a ed Chi osan Nanopa icles o Lung Tumo Ta ge ing: Imp o ing The apeu ic E icacy Bo h in Vi o and in Vi o. Onco a ge 2017,8, 111318–111332. [C ossRe ] 159. Almajidi, Y.Q.; Ma aie, N.K.; Raau , A.M.R. Modi ied Solid in Oil Nanodispe sion Con aining Vemu a enib-Lipid Complex-in Vi o/in Vi o S udy. F1000Resea ch 2022,11, 841. [C ossRe ] [PubMed] 160. Fu, Y.; Sa aswa , A.; Wei, Z.; Ag awal, M.Y.; Dukhande, V.V.; Reznik, S.E.; Pa el, K. De elopmen o Dual A -825 and Nin edanib- Loaded Pegyla ed Nano-Liposomes o Syne gis ic E icacy in Vemu a nib-Resis an Melanoma. Pha maceu ics 2021 ,13, 1005. [C ossRe ] 161. Xia, L.; Kong, X.; Liu, X.; Tu, L.; Zhang, Y.; Chang, Y.; Liu, K.; Shen, D.; Zhao, H.; Zhang, H. An Upcon e sion Nanopa icle—Zinc Ph halocyanine Based Nanopho osensi ize o Pho odynamic The apy. Bioma e ials 2014,35, 4146–4156. [C ossRe ] 162. Yu , F.; Ocakoglu, K.; Ince, M.; Colak, S.G.; E , O.; Soylu, H.M.; Gunduz, C.; Bi ay A ci, C.; Caliskan Ku , C. Pho odynamic The apy and Nuclea Imaging Ac i i ies o Zinc Ph halocyanine-In eg a ed TiO 2 Nanopa icles in B eas and Ce ical Tumo s. Chem. Biol. D ug Des. 2018,91, 789–796. [C ossRe ] Disclaime /Publishe ’s No e: The s a emen s, opinions and da a con ained in all publica ions a e solely hose o he indi idual au ho (s) and con ibu o (s) and no o MDPI and/o he edi o (s). 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