Review on nanomedicine and phytotherapy for cancer

*Corresponding author: M. Bharath kumar Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution License 4.0. Review on nanomedicine and phytotherapy for cancer M. Bharath kumar 1, *, P Sailaja 2 and Y. Prapurnachandra 2 1 Department of Pharmacy, Ratnam Institute of Pharmacy, Pidathapolur (V), Muthukur (M), SPSR Nellore Dt. 524346 A.P. India. 2 Department of Pharmacology, Ratnam Institute of Pharmacy, Pidathapolur (V), Muthukur (M), SPSR Nellore Dt. 524346 A P. India. World Journal of Biology Pharmacy and Health Sciences, 2025, 24(02), 240-250 Publication history: Received on 11 September 2025; revised on 24 October 2025; accepted on 28 October 2025 Article DOI: https://doi.org/10.30574/wjbphs.2025.24.2.0915 Abstract Cancer is well recognized as a leading cause of mortality. Although surgery tends to be the primary treatment option for many solid cancers, cancer surgery is still a risk factor for metastatic diseases and recurrence. For this reason, a variety of medications has been adopted for the postsurgical care of patients with cancer. However, conventional medicines have shown major challenges such as drug resistance, a high level of drug toxicity, and different drug responses, due to tumor heterogeneity. Nanotechnology-based therapeutic formulations could effectively overcome the challenges faced by conventional treatment methods. In particular, the combined use of nanomedicine with natural phytochemicals can enhance tumor targeting and increase the efficacy of anticancer agents with better solubility and bioavailability and reduced side effects. However, there is limited evidence in relation to the application of phytochemicals in cancer treatment, Particularly focusing on nanotechnology, therefore, in this review, first, we introduce the drug carriers used in advanced nanotechnology and their strengths and limitations. Second, we provide an update on well-studied nanotechnologybased anticancer therapies related to the carcinogenesis process, including signaling pathways related to transforming growth factor-β (TGF-β), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3 kinase (PI3K), Wnt, poly(ADP-ribose) polymerase (PARP), Notch, and Hedgehog (HH). Third, we introduce approved nanomedicines currently available for anticancer therapy. Fourth, we discuss the potential roles of natural phytochemicals as anticancer drugs. Fifth, we also discuss the synergistic effect of nanocarriers and phytochemicals in anticancer therapy. Keywords: Cancer; Postoperative anticancer therapy; Nanotechnology; Nanomedicine; Phytochemicals 1. Introduction It is often known that one of the main causes of death is cancer. Globally, there were an estimated 10.3 million cancerrelated deaths and 19.3 million new cancer diagnoses in 2020.. The most common new case was breast cancer, which was followed by skin, stomach, colon, lung, and prostate cancers1.Even though surgery is frequently the first line of treatment for solid tumors, numerous clinical and experimental investigations have shown that cancer surgery increases the risk of metastatic illnesses and recurrence. The perioperative period after cancer surgery is crucial for determining the risk of postoperative metastatic diseases and provides a window of opportunity for treatment against lingering malignant illness2. For this reason, a variety of medications has been adopted for the postsurgical care of patientswith cancer3. However, there have been significant problems with conventional treatments, including drug resistance, high levels of drug toxicity, and varying drug responses because of tumor heterogeneity. A viable alternative to increase the World Journal of Biology Pharmacy and Health Sciences, 2025, 24(02), 240-250 241 effectiveness and selectivity of anticancer medications in anticancer therapy has recently been proposed: a therapeutic approach based on nanomedicin4.Therapeutic medications based on nanomedicines can regulate the local and systemic release of medications, improving therapy efficacy, lowering toxicity, and improving patient outcomes by helping to target tumor sites. Tumor-targeted nanoparticle (NP)-based anticancer therapy, in particular, is regarded as a broad and advantageous era in cancer biology5. For patients with cancer at various stages, surgery, chemotherapy, and radiation therapy have been common first-line treatment choices. Most cancer patients are treated with chemotherapy either before to or following surgery. Chemotherapeutic drugs target fast-dividing malignant cells, but they also impact healthy cells that replicate quickly, like those found in the gastrointestinal tract, hair follicles, and bone marrow. Chemotherapy damages organs and systems through a variety of ways, including as direct toxicity, indirect toxicity caused by liver metabolites, immune system suppression, decreased oxygen delivery, and inflammation. The organs and systems impacted determine the precise negative consequences and damage manifestation6 Lung cancer and prostate cancer are the most common cancers in men, with 1.37 million and 1.28 million cases, respectively. Lung cancer, which affects 1.37 million people, and prostate cancer, which affects 1.28 million people, come next in terms of stomach and liver cancer. With 0.68 and 0.60 million instances, respectively, stomach and liver cancer rank third and fourth after these. With 2.09 million instances documented, breast cancer is the most common type of cancer in women, according to Gonzalez-Valdivieso et al. The next most common cancers are lung cancer (0.72 million patients), cervix uteri cancer (0.57 million cases), and colon cancer (0.58 million cases reported)7. 2. Types of cancer Table 1 Types of cancer Type of cancer Origin / Affected Tissue Common Examples Major Risk Factors Common Symptoms Main Treatment Option 1 Carcinoma Epithelial cells (lining of organs, glands, skin) Breast, Lung, Prostate, Colon, Skin cancer Smoking, radiation, viral infections (HPV), genetics Lump, pain, bleeding, weight loss Surgery, Chemotherapy, Radiotherapy, Immunotherapy 2 Sarcoma Connective tissues (bone, muscle, fat, cartilage) Osteosarcoma, Liposarcoma, Leiomyosarcom a Radiation exposure, genetic disorders, chronic lymphedem a Pain, swelling, mass in limb or trunk Surgery, Radiation therapy, Chemotherapy 3 Leukemia Blood-forming tissues (bone marrow) Acute Lymphoblastic Leukemia (ALL), Chronic Myeloid Leukemia (CM Radiation, benzene exposure, genetic mutations Fatigue, frequent infections, bleeding, anemia Chemotherapy, Bone marrow transplant, Targeted t 4 Lymphom a Lymphatic system (lymph nodes, spleen) Hodgkin’s Lymphoma, Non-Hodgkin’s Lymphoma Viral infections (EBV, HIV), immune suppression Swollen lymph nodes, fever, night sweats, weight loss Chemotherapy, Radiation, Immunotherapy 5 Melanoma Melanocytes (pigmentproducing skin cells) Cutaneous melanoma UV radiation, fair skin, Moles that change Surgery, Immunotherapy World Journal of Biology Pharmacy and Health Sciences, 2025, 24(02), 240-250 242 family history color/shape , skin lesions , Targeted therapy 6 Myeloma Plasma cells (in bone marrow) Multiple Myeloma Age, radiation exposure, family history Bone pain, anemia, kidney problems Chemotherapy, Targeted therapy, Stem cell transplant 3. Pathophysiology of Cancer Figure 1 Pathophysiology of Cancer 3.1. Mutation Inactivates Tumor Suppressor Gene Normally, tumor suppressor genes (such as p53, RB, and BRCA1) regulate cell growth and stop aberrant division. Cells lose their ability to regulate their growth and begin to divide uncontrollably when a mutation renders these genes inactive. As an illustration, injured cells cannot undergo apoptosis when p53 activity is lost. 3.2. Cells Begin to Proliferate When tumor suppressor genes are deactivated, the cells divide erratically, aggregating into a cluster of fast-dividing cells that are immune to the regular signals that control the cell cycle. 3.3. Mutation Inactivates DNA Repair Genes Genes that repair DNA, such as MLH1 and MSH2, correct mistakes made during DNA replication. When these genes are mutated, more DNA mistakes are produced, hastening the development of cancer. World Journal of Biology Pharmacy and Health Sciences, 2025, 24(02), 240-250 243 3.4. Mutation of Proto-Oncogene Creates an Oncogenes • Normally, proto-oncogenes (such RAS, MYC, and HER2) encourage regulated cell division. • They become oncogenes through mutation, which promotes unchecked cell division. • Even in the absence of growth factors, this leads to increased signaling for cell division. 3.5. Additional Mutations Inactivate More Tumor Suppressor Genes Over time, a number of genetic changes build up, and more growth, invasion, and apoptosis resistance are made possible by the inactivation of extra tumor suppressor genes. 3.6. Formation of Cancer (Malignant Tumor) When these mutations combine, the result is a malignant phenotype, which consists of cells that proliferate out of control, infiltrate nearby tissues, and have the potential to spread to other bodily areas.These malignant cells develop the following abilities: 3.7. Persistent signaling for proliferation Inducing angiogenesis (the development of new blood vessels) o Resistance to cell deathForm Bottom8. 4. Treatment of Cancer 4.1. Treatments by surgery The primary goal of surgical treatment for cancer is to remove the entire tumor that is located in one region, or to remove the tumor partially (if complete removal could harm an organ or the body) so that other treatments can function more effectively, or to eliminate the tumors that are causing pain.Over the past century, the use of surgery in cancer treatment has changed significantly and expanded due to advances in technologies and growing knowledge of cancer from the perspectives of genetics, molecular biology, and tumor immunology. Historically, surgery was the first line of defense against a tumor and was thought to be the sole effective treatment for cancer. However, the growing use of neoadjuvant medicines has frequently made surgery a second or third line of treatment9,10. 4.2. Treatments using chemotherapy One or more anti-cancer medications (chemotherapeutic agents) are used in chemotherapy to stop or limit the growth of rapidly dividing cancer cells, reduce the likelihood that the cancer will return, alleviate cancer symptoms, reduce the size of tumors that are causing discomfort, and other issues. In order to prevent mitotic cell division or cause DNA damage, chemotherapy uses non-specific intracellular poisons. By preventing DNA repair, chemotherapy can be improved. Earlier attempts to increase the effectiveness of treatment by creating different combinations of cytotoxic drugs have yielded unsatisfactory outcomes with high mortality11. Chemotherapy has become increasingly useful in recent years for treating cancer because it can precisely target and kill tumor cells while sparing healthy ones. This revolution has promise for enhancing cancer therapy efficacy and tolerance, which will eventually improve patient outcomes12. 4.3. Treatments using hormonal therapy All multicellular creatures have several organs and glands that generate hormones, which are signaling molecules that can be proteins or other substances that are transferred to distant organs to govern cell function, physiology, and/or behavior. The body uses hormones for a variety of purposes, and some types of cancer rely on hormones to flourish. The growth of cancers can therefore be slowed or stopped by inhibiting or changing hormone actions. Hormone-based cancer treatment is mostly utilized for prostate and breast cancers that rely on sex hormones for growth. Because the medications used to target hormones move throughout the body in search of the hormones, hormone therapy is regarded as a systemic treatment. Because they only affect one area of the body, these treatments are referred to as local treatments. Additionally, surgeries are done to remove organs that produce hormones13. World Journal of Biology Pharmacy and Health Sciences, 2025, 24(02), 240-250 244 4.4. Treatment by radiation Ionizing radiation is used in radiation therapy, often known as radiotherapy for cancer, to control or destroy cancerous cells. It is typically administered using a linear accelerator. Low amounts of radiation are used in x-rays to view within the body, such as for x-rays of fractured bones or teeth, whereas high doses are used to destroy cancer cells and shrink tumors. If radiation therapy is applied to a single part of the body, it may be able to cure a variety of cancer forms. In the early stages of pancreatic and breast cancer, for instance, it may be administered as part of adjuvant therapy to prevent tumor recurrence following surgical removal of the main malignant tumor14,15. 5. Nanomedicine for cancer The use of nanosized materials to deliver anticancer medications straight to tumor cells enhances treatment precision while reducing harm to healthy tissues16. This technique is known as nanomedicine for cancer. 5.1. Molecular mechanism of nanomedicine for cancer The ability of a nanomedicine formulation to specifically target cancer tissue while causing the least amount of adverse effects on healthy tissue is a crucial consideration for choosing one for cancer treatment. Different targeting strategies are employed by the different nano-formulations that deliver anticancer medications to tumor locations. Each carrier will have a unique drug delivery method and set of benefits. Therapeutic chemicals are delivered to the targeted location and bloodstream directly using nanocarriers. They then overproduce reactive oxygen species (ROS), which damages DNA. For nano-based medication delivery, two main targeting technique types are employed: passive and active17. The passive approach focuses the nano-vehicles on the tumor site by utilizing its characteristics. The characteristics of the tumor microenvironment (TME) and enhanced permeability and retention (EPR) are the main criteria exploited for this. Tumor cells, in contrast to normal cells, cause neovascularization because of their rapid rate of proliferation and the wide vascular wall pores that facilitate passive targeting. Inadequate angiogenesis can allow particles to enter the tumor location and build up. EPR on tumors is caused by poor lymphatic outflow, which also enhances particle retention. However, the tumor microenvironment's high interstitial fluid pressure inhibits nanoparticle absorption and uniform distribution18. Figure 2 Passive targeting However, nanoparticles preferentially aggregate in tumor tissue to a greater extent than in normal tissuedue to the heightened permeability and retention impact of tumor tissue. Heterogeneous distribution of nanoparticles, which are mostly seen in the perivascular area and tumor periphery, is often caused by the aberrant and dysfunctional tumor microenvironment. For consistent medication delivery throughout the tumor, several nanocarriers also make use of the TME's characteristics, such as its acidic pH, elevated redox potential, and variable production of lytic enzymes. Additionally, active targeting makes use of the characteristics of the tumor cells, such as the cell surface receptors that World Journal of Biology Pharmacy and Health Sciences, 2025, 24(02), 240-250 245 the cancer cells express. However, in order to target these molecules selectively, a variety of molecules are hybridized with the carrier. Here, we examine the various targeting strategies employed by the different nano-formulations, along with some of their benefits and drawbacks19. Figure 3 Active targeting Generally speaking, passive targeting relies on the diffusion mechanism and is influenced by a number of variables, including surface characteristics, size, and shape. It has been observed that by lengthening the circulation duration, 40 to 400 nm can produce high bioavailability and decreased renal clearance. Similarly, keeping the particles stiff and spherical and in the 50–200 particle size range prolongs circulation and lowers kidney clearance20. Uneven neovascularization, increased inflammatory factor production, and an ineffective lymphatic drainage system were characteristics of tumor cells. 6. Advantages and disadvantages nanomedicine in cancer treatment 6.1. Advantages • Targeted Drug Delivery: By precisely delivering anticancer medications straight to tumor cells, nanomedicine lessens the harm done to healthy tissues. • Increased Bioavailability of Drugs: Nanoparticles increase the therapeutic impact of poorly soluble medications by improving their solubility, stability, and absorption. • Decreased Side Effects: Nanomedicine reduces systemic toxicity and unpleasant effects by concentrating medications in the tumor site21. • Controlled and Sustained Release:Drugs can be released from nanocarriers gradually and steadily, extending the time that they remain effective. 6.2. Disadvantages: • Expensive and Complex Manufacturing: Producing and characterizing nanomedicines calls for sophisticated equipment and is frequently costly. • Issues with biocompatibility and toxicity: Certain nanoparticles pose long-term safety issues because they can build up in organs or induce unforeseen toxicity. • Limited Clinical Translation: Although many nanomedicines perform well in lab tests, they have trouble transitioning to widespread clinical application22. • Quick Immune System Clearance:The body may identify and eliminate nanoparticles before they reach the tumor, which lowers the effectiveness of treatment23. World Journal of Biology Pharmacy and Health Sciences, 2025, 24(02), 240-250 246 7. Phytotherapy for cancer The use of substances produced from plants (phytochemicals) to treat or prevent illnesses, including cancer, is known as phytotherapy. Numerous phytochemicals exhibit anticancer effects through a variety of molecular pathways. They can be used in conjunction with regular therapies and are frequently less harmful than traditional chemotherapy. Since ancient times, herbal remedies have been utilized to cure a variety of ailments. Herbs have long been used as medicines in nations like Greece and India, and many contemporary medications are made from these organic materials24. The Sumerians and Akkadians had the first written records of the use of therapeutic plants circa 2600 BC. 8. Molecular mechanism of phytotherapy for cancer Natural compounds have shown anticancer benefits through a variety of methods of action in exhibiting anticancer effects. Figure 4 Mechanisms of natural products in cancer prevention Table 2 List of phytochemicals used in cancer S.NO Source of Phytochemical Chemical Structure Experimental Model Action Mechanism of Phytochemical 1 Lipopolysaccharideinduced BV-2 microglial cells Inhibit the production of proinflammatory mediators by inhibiting MAPK and I-kappa B kinase (IKK)-dependent NFκBsignaling pathway World Journal of Biology Pharmacy and Health Sciences, 2025, 24(02), 240-250 247 Erigeron breviscapus Scutellarin 2 Blackcumin seed of Nigella sativa Thymoquinone Lipopolysaccharideinduced BV-2 microglial cells Inhibit NFκB-dependent neuroinflammation in BV2 microglia via activating the antioxidant response element (ARE)/nuclear erythroid 2 related factor 2 (Nrf2) antioxidant pathway 3 Artocarpuslakoo Oxyresveratrol Human microglial cells Exerts anti-inflammatory roles in IL-1β-induced human microglial clone 3 cells by inhibiting extracellular signal-regulated kinases (ERKs) on MAPK signaling cascades and the AKT25 4 Abiesholophylla Terpenoids Lipopolysaccharideactivated BV2 murine microglial cells Exert neuroprotective and antiinflammatory effects by decreasing production of nitrite and increasing the production of nerve growth factor through the inhibition of JNK phosphorylation, thereby inhibiting the secretion of proinflammatory cytokines such as IL-1β, IL-6, TNF, and prostaglandin E2, and effectively decreasing neuroinflammation 5 Curcuma longa Curcumin Head and neck squamous carcinoma cells, TLR4(-/-) or wild type of subarachnoid hemorrhage-induced mice model Possesses antioxidant, anticancer, and anti-inflammatory effects. Decrease neuroinflammation postsubarachnoid hemorrhage by inhibiting toll-like receptor/NFκBsignaling pathway and sequentially a shift of microglia M1 phenotype to M2, which promotes tumor survival 6 Moringa oleifera see Moringin Autoimmune encephalomyelitis mice model Normalize the Wnt/β-catenin signaling pathway. Upregulate βcatenin and inhibit glycogen synthase kinase-3, which leads to the regulation of FoxP3 and CD4 expression in T cell activation, inhibition of COX-2, IL-6, and IL1β, decreased apoptosis, and increased expression of antioxidant Nrf2 World Journal of Biology Pharmacy and Health Sciences, 2025, 24(02), 240-250 248 9. Advantages and disadvantages of Phytotherapy in cancer treatment: 9.1. Advantages: • Natural Origin: Compared to many synthetic medications, phytotherapy uses substances derived from plants, which are typically safer and less poisonous. • • Several Action Mechanisms: Plant chemicals are effective against complex cancer processes because they can target multiple biological pathways at once, including immune modulation, angiogenesis suppression, and apoptosis induction26,27. • Decreased Adverse Reactions: When compared to chemotherapy and radiation, herbal remedies frequently have less side effects, increasing patient tolerance and quality of life. 9.2. Disadvantages: • Lack of Standardization: Herbal extracts' active ingredient concentrations and purity can differ, producing uneven therapeutic results28. • Insufficient Clinical Data: Few extensive human clinical trials have confirmed the safety and efficacy of phytotherapeutic effects; the majority are backed by in vitro or animal investigations29,30. • Low Bioavailability: The body's ability to use many phytochemicals is diminished by their low solubility, poor absorption, and quick metabolism31. 10. Conclusion Two promising and complementary strategies for treating cancer in the current era are phytotherapy and nanomedicine. Natural plant chemicals that have been shown anticancer effects including apoptosis induction, angiogenesis inhibition and inflammation reduction, are used in phytotherapy. However, their clinical efficacy is limited by issues such as low bioavailability and poor solubility. These obstacles are addressed by nanomedicine by using sophisticated nanocarriers to improve stability, minimize adverse effects, and improve targeted delivery. Combining the accuracy and effectiveness of nanotechnology with the inherent medicinal potential of plant chemicals is known as nano-phytotherapy. In addition to improving cancer treatment effectiveness, this synergistic approach provides a more secure and patient-friendly substitute for traditional medicines. For these novel treatments to become successful cancer medicines for use in future medical procedures, more investigation, standardization, and clinical validation are necessary. Compliance with ethical standards Disclosure of conflict of interest No conflict of interest associated with this work. Contribution of Authors The authors declare that this review work was done by the authors named in this article and all liabilities pertaining to claims relating to the content of this article will be borne by them. 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