Authors : Shriya Pande; Vidya Sabale

Volume/Issue : Volume 10 - 2025, Issue 4 - April

Google Scholar : https://tinyurl.com/muhcjdr7

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DOI : https://doi.org/10.38124/ijisrt/25apr1139

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Abstract : This comprehensive review highlights the recent advances in nanocarrier-mediated delivery of plant-derived phytoconstituents for cancer treatment. Various nanocarriers such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, dendrimers, nanoemulsions, and metallic nanoparticles are discussed in terms of their design, functionalization, and role in improving pharmacokinetics, stability, tumor targeting, and controlled release of phytoconstituents. The synergistic potential of co-delivery systems, surface modification strategies (e.g., PEGylation, ligand conjugation), and stimuli-responsive nanocarriers are also elaborated. Furthermore, the review explores in vitro and in vivo studies demonstrating enhanced anticancer efficacy, reduced systemic toxicity, and improved therapeutic index of phytoconstituents via nano delivery. Key challenges in clinical translation such as large-scale manufacturing, regulatory approval, and safety profiling are addressed along with future directions. Overall, nanocarrier-based strategies represent a promising frontier for integrating phytomedicine into mainstream oncology, enabling targeted, safe, and effective cancer therapy. This review aims to provide researchers, formulators, and clinicians with a foundational understanding of the nanotechnological advancements driving the next generation of plant-based anticancer therapeutics.

References :

1. Akanda, Mushfiq, MD Sadeque Hossain Mithu, and Dennis Douroumis. 2023. “Solid Lipid Nanoparticles: An Effective Lipid-Based Technology for Cancer Treatment.” Journal of Drug Delivery Science and Technology. https://doi.org/10.1016/j.jddst.2023.104709.
2. Alghamdi, Ali Hendi, Aimun A.E. Ahmed, Haidar Abdalgadir, Mahadi Bashir, Asaad Khalid, Ashraf N. Abdalla, Mohamed E. Elzubier, et al. 2024. “In-Vitro Cytotoxicity Investigations for Phytoconstituents of Saudi Medicinal Plants With Putative Ocular Effects.” Integrative Cancer Therapies 23. https://doi.org/10.1177/15347354241256649.
3. Almeida, Andreia, Bruno Sarmento, and Francisca Rodrigues. 2017. “Insights on in Vitro Models for Safety and Toxicity Assessment of Cosmetic Ingredients.” International Journal of Pharmaceutics 519 (1–2): 178–85. https://doi.org/10.1016/j.ijpharm.2017.01.024.
4. Arora, Sumit, Jyutika M. Rajwade, and Kishore M. Paknikar. 2012. “Nanotoxicology and in Vitro Studies: The Need of the Hour.” Toxicology and Applied Pharmacology 258 (2): 151–65. https://doi.org/10.1016/j.taap.2011.11.010.
5. Baby, Jasmine, Aswathy R. Devan, Ayana R. Kumar, Jaggaiah N. Gorantla, Bhagyalakshmi Nair, Thanatharayil Sathian Aishwarya, and Lekshmi R. Nath. 2021. “Cogent Role of Flavonoids as Key Orchestrators of Chemoprevention of Hepatocellular Carcinoma: A Review.” Journal of Food Biochemistry 45 (7). https://doi.org/10.1111/jfbc.13761.
6. Beg, Sarwar, Mahfoozur Rahman, and Kanchan Kohli. 2019. “Quality-by-Design Approach as a Systematic Tool for the Development of Nanopharmaceutical Products.” Drug Discovery Today 24 (3): 717–25. https://doi.org/10.1016/j.drudis.2018.12.002.
7. Bhalani, Dixit V., Bhingaradiya Nutan, Avinash Kumar, and Arvind K. Singh Chandel. 2022. “Bioavailability Enhancement Techniques for Poorly Aqueous Soluble Drugs and Therapeutics.” Biomedicines 10 (9). https://doi.org/10.3390/biomedicines10092055.
8. Cattley, Russell C., and Robert R. Radinsky. 2004. “Cancer Therapeutics: Understanding the Mechanism of Action.” Toxicologic Pathology 32 (SUPPL. 1): 116–21. https://doi.org/10.1080/01926230490426507.
9. Chehelgerdi, Mohammad, Matin Chehelgerdi, Omer Qutaiba B. Allela, Renzon Daniel Cosme Pecho, Narayanan Jayasankar, Devendra Pratap Rao, Tamilanban Thamaraikani, et al. 2023. “Progressing Nanotechnology to Improve Targeted Cancer Treatment: Overcoming Hurdles in Its Clinical Implementation.” Molecular Cancer 22 (1). https://doi.org/10.1186/s12943-023-01865-0.
10. Chen, Huabing, Zhanjun Gu, Hongwei An, Chunying Chen, Jie Chen, Ran Cui, Siqin Chen, et al. 2018. “Precise Nanomedicine for Intelligent Therapy of Cancer.” Science China Chemistry 61 (12): 1503–52. https://doi.org/10.1007/s11426-018-9397-5.
11. Cordaillat-Simmons, Magali, Alice Rouanet, and Bruno Pot. 2020. “Live Biotherapeutic Products: The Importance of a Defined Regulatory Framework.” Experimental and Molecular Medicine 52 (9): 1397–1406. https://doi.org/10.1038/s12276-020-0437-6.
12. Darvishi, Mohammad, Foad Tosan, Pooria Nakhaei, Danial Amiri Manjili, Sahar Afzali Kharkouei, Ali Alizadeh, Saba Ilkhani, Farima Khalafi, Firoozeh Abolhasani Zadeh, and Seyyed Ghavam Shafagh. 2023. “Recent Progress in Cancer Immunotherapy: Overview of Current Status and Challenges.” Pathology Research and Practice 241 (November). https://doi.org/10.1016/j.prp.2022.154241.
13. Ferreira, Mara, Luísa Barreiros, Marcela A. Segundo, Tiago Torres, Manuela Selores, Sofia A. Costa Lima, and Salette Reis. 2017. “Topical Co-Delivery of Methotrexate and Etanercept Using Lipid Nanoparticles: A Targeted Approach for Psoriasis Management.” Colloids and Surfaces B: Biointerfaces 159. https://doi.org/10.1016/j.colsurfb.2017.07.080.
14. Freag, May S., Wedad M. Saleh, and Ossama Y. Abdallah. 2018. “Self-Assembled Phospholipid-Based Phytosomal Nanocarriers as Promising Platforms for Improving Oral Bioavailability of the Anticancer Celastrol.” International Journal of Pharmaceutics 535 (1–2): 18–26. https://doi.org/10.1016/j.ijpharm.2017.10.053.
15. Gao, Quan, Jiao Feng, Wencheng Liu, Chengyong Wen, Yihan Wu, Qian Liao, Liang Zou, et al. 2022. “Opportunities and Challenges for Co-Delivery Nanomedicines Based on Combination of Phytochemicals with Chemotherapeutic Drugs in Cancer Treatment.” Advanced Drug Delivery Reviews 188: 114445. https://doi.org/10.1016/j.addr.2022.114445.
16. Garcia-Oliveira, Paula, Paz Otero, Antia Gonzalez Pereira, Franklin Chamorro, Maria Carpena, Javier Echave, Maria Fraga-Corral, Jesus Simal-Gandara, and Miguel Angel Prieto. 2021. “Status and Challenges of Plant-Anticancer Compounds in Cancer Treatment.” Pharmaceuticals 14 (2): 1–28. https://doi.org/10.3390/ph14020157.
17. Gilani, Sadaf Jamal, Sarwar Beg, Chandra Kala, Mohammed Shivli Nomani, Debarshi Kar Mahapatra, Syed Sarim Imam, and Mohamad Taleuzzaman. 2019. “Chemically Nano-Engineered Theranostics for Phytoconstituents as Healthcare Application.” Current Biochemical Engineering 6 (1): 53–61. https://doi.org/10.2174/2212711906666190723144111.
18. Gothai, Sivapragasam, Palanivel Ganesan, Shin Young Park, Sharida Fakurazi, Dong Kug Choi, and Palanisamy Arulselvan. 2016. “Natural Phyto-Bioactive Compounds for the Treatment of Type 2 Diabetes: Inflammation as a Target.” Nutrients 8 (8). https://doi.org/10.3390/nu8080461.
19. Gulia, Khushabu, Abija James, Sadanand Pandey, Kamal Dev, Deepak Kumar, and Anuradha Sourirajan. 2022. “Bio-Inspired Smart Nanoparticles in Enhanced Cancer Theranostics and Targeted Drug Delivery.” Journal of Functional Biomaterials 13 (4). https://doi.org/10.3390/jfb13040207.
20. Handa, Mayank, Sarwar Beg, Rahul Shukla, Md Abul Barkat, Hani Choudhry, and Kamalinder K. Singh. 2021. “Recent Advances in Lipid-Engineered Multifunctional Nanophytomedicines for Cancer Targeting.” Journal of Controlled Release 340 (October): 48–59. https://doi.org/10.1016/j.jconrel.2021.10.025.
21. Huang, Min, Jin Jian Lu, and Jian Ding. 2021. “Natural Products in Cancer Therapy: Past, Present and Future.” Natural Products and Bioprospecting 11 (1): 5–13. https://doi.org/10.1007/s13659-020-00293-7.
22. Imperiale, Julieta C., Gabriela B. Acosta, and Alejandro Sosnik. 2018. “Polymer-Based Carriers for Ophthalmic Drug Delivery.” Journal of Controlled Release 285: 106–41. https://doi.org/10.1016/j.jconrel.2018.06.031.
23. kazemi, S., A. Hosseingholian, S. D. Gohari, F. Feirahi, F. Moammeri, G. Mesbahian, Z. S. Moghaddam, and Q. Ren. 2023. “Recent Advances in Green Synthesized Nanoparticles: From Production to Application.” Materials Today Sustainability 24: 100500. https://doi.org/10.1016/j.mtsust.2023.100500.
24. Leenes, Ronald, Erica Palmerini, Bert Jaap Koops, Andrea Bertolini, Pericle Salvini, and Federica Lucivero. 2017. “Regulatory Challenges of Robotics: Some Guidelines for Addressing Legal and Ethical Issues.” Law, Innovation and Technology 9 (1): 1–44. https://doi.org/10.1080/17579961.2017.1304921.
25. Legido-Quigley, Helena, Dimitra Panteli, Serena Brusamento, Cécile Knai, Vanessa Saliba, Eva Turk, Meritxell Solé, et al. 2012. “Clinical Guidelines in the European Union: Mapping the Regulatory Basis, Development, Quality Control, Implementation and Evaluation across Member States.” Health Policy 107 (2–3): 146–56. https://doi.org/10.1016/j.healthpol.2012.08.004.
26. Lin, Sen, Peiling Xie, Mengmeng Luo, Qing Li, Ling Li, Jinzhao Zhang, Qinxiang Zheng, Hao Chen, and Kaihui Nan. 2018. “Efficiency against Multidrug Resistance by Co-Delivery of Doxorubicin and Curcumin with a Legumain-Sensitive Nanocarrier.” Nano Research 11 (7): 3619–35. https://doi.org/10.1007/s12274-017-1928-1.
27. Liu, Yarong, Jinxu Fang, Yu Jeong Kim, Michael K. Wong, and Pin Wang. 2014. “Codelivery of Doxorubicin and Paclitaxel by Cross-Linked Multilamellar Liposome Enables Synergistic Antitumor Activity.” Molecular Pharmaceutics 11 (5): 1651–61. https://doi.org/10.1021/mp5000373.
28. Mehta, Rajendra G., Genoveva Murillo, Rajesh Naithani, and Xinjian Peng. 2010. “Cancer Chemoprevention by Natural Products: How Far Have We Come?” Pharmaceutical Research 27 (6): 950–61. https://doi.org/10.1007/s11095-010-0085-y.
29. Mir, Manzoor A., Hina Qayoom, Umar Mehraj, Safura Nisar, Basharat Bhat, and Nissar A. Wani. 2020. “Targeting Different Pathways Using Novel Combination Therapy in Triple Negative Breast Cancer.” Current Cancer Drug Targets 20 (8): 586–602. https://doi.org/10.2174/1570163817666200518081955.
30. Nakonieczna, Sylwia, Aneta Grabarska, and Wirginia Kukula‐koch. 2020. “The Potential Anticancer Activity of Phytoconstituents against Gastric Cancer—a Review on in Vitro, in Vivo, and Clinical Studies.” International Journal of Molecular Sciences 21 (21): 1–27. https://doi.org/10.3390/ijms21218307.
31. Niesen, Willem, Thomas Hank, Markus Büchler, and Oliver Strobel. 2019. “Local Radicality and Survival Outcome of Pancreatic Cancer Surgery.” Annals of Gastroenterological Surgery 3 (5): 464–75. https://doi.org/10.1002/ags3.12273.
32. Noreen, Sobia, Shazma Ehsan, Shazia Akram Ghumman, Sara Hasan, Fozia Batool, Bushra Ijaz, Bahareh Shirinfar, Khadeeja Ali Mohammed Alsader, and Nisar Ahmed. 2023. “Polymeric Complex Nanocarriers of Mangifera Indica Gum & Chitosan for Methotrexate Delivery: Formulation, Characterization, and in Vitro Toxicological Assessment.” Journal of Drug Delivery Science and Technology 88. https://doi.org/10.1016/j.jddst.2023.105001.
33. Porter, Christopher J.H., Natalie L. Trevaskis, and William N. Charman. 2007. “Lipids and Lipid-Based Formulations: Optimizing the Oral Delivery of Lipophilic Drugs.” Nature Reviews Drug Discovery 6 (3): 231–48. https://doi.org/10.1038/nrd2197.
34. Psimadas, Dimitrios, Panagiotis Georgoulias, Varvara Valotassiou, and George Loudos. 2012. “Molecular Nanomedicine Towards Cancer :” Journal of Pharmaceutical Sciences 101 (7): 2271–80. https://doi.org/10.1002/jps.
35. Rapoport, Bernardo L., and Ronald Anderson. 2019. “Realizing the Clinical Potential of Immunogenic Cell Death in Cancer Chemotherapy and Radiotherapy.” International Journal of Molecular Sciences 20 (4): 1–27. https://doi.org/10.3390/ijms20040959.
36. Rosenblum, Daniel, Nitin Joshi, Wei Tao, Jeffrey M. Karp, and Dan Peer. 2018. “Progress and Challenges towards Targeted Delivery of Cancer Therapeutics.” Nature Communications 9 (1). https://doi.org/10.1038/s41467-018-03705-y.
37. Salaria, Deeksha, Rajan Rolta, Jyoti Mehta, Oladoja Awofisayo, Olatomide A. Fadare, Baljinder Kaur, Balvir Kumar, et al. 2022. “Phytoconstituents of Traditional Himalayan Herbs as Potential Inhibitors of Human Papillomavirus (HPV-18) for Cervical Cancer Treatment: An In Silico Approach.” PLoS ONE 17 (3 March): 1–20. https://doi.org/10.1371/journal.pone.0265420.
38. Shrihastini, Vijayakumar, Pandiyan Muthuramalingam, Sivakumar Adarshan, Mariappan Sujitha, Jen Tsung Chen, Hyunsuk Shin, and Manikandan Ramesh. 2021. “Plant Derived Bioactive Compounds, Their Anti‐cancer Effects and in Silico Approaches as an Alternative Target Treatment Strategy for Breast Cancer: An Updated Overview.” Cancers 13 (24). https://doi.org/10.3390/cancers13246222.
39. Sistare, Frank D., Daniel Morton, Carl Alden, Joel Christensen, Douglas Keller, Sandra De Jonghe, Richard D. Storer, et al. 2011. “An Analysis of Pharmaceutical Experience with Decades of Rat Carcinogenicity Testing: Support for a Proposal to Modify Current Regulatory Guidelines.” Toxicologic Pathology 39 (4): 716–44. https://doi.org/10.1177/0192623311406935.
40. Sutton, Damon, Norased Nasongkla, Elvin Blanco, and Jinming Gao. 2007. “Functionalized Micellar Systems for Cancer Targeted Drug Delivery.” Pharmaceutical Research 24 (6): 1029–46. https://doi.org/10.1007/s11095-006-9223-y.
41. Tahir, Nayab, Asadullah Madni, Vimalkumar Balasubramanian, Mubashar Rehman, Alexandra Correia, Prince Muhammad Kashif, Ermei Mäkilä, Jarno Salonen, and Hélder A. Santos. 2017. “Development and Optimization of Methotrexate-Loaded Lipid-Polymer Hybrid Nanoparticles for Controlled Drug Delivery Applications.” International Journal of Pharmaceutics 533 (1). https://doi.org/10.1016/j.ijpharm.2017.09.061.
42. Vaou, Natalia, Elisavet Stavropoulou, Chrysoula Voidarou, Zacharias Tsakris, Georgios Rozos, Christina Tsigalou, and Eugenia Bezirtzoglou. 2022. “Interactions between Medical Plant-Derived Bioactive Compounds: Focus on Antimicrobial Combination Effects.” Antibiotics 11 (8): 1–23. https://doi.org/10.3390/antibiotics11081014.
43. Wang, Yawei, Haiyan Zhang, Jing Hao, Bei Li, Ming Li, and Wang Xiuwen. 2016. “Lung Cancer Combination Therapy: Co-Delivery of Paclitaxel and Doxorubicin by Nanostructured Lipid Carriers for Synergistic Effect.” Drug Delivery 23 (4): 1398–1403. https://doi.org/10.3109/10717544.2015.1055619.
44. Wiecek, Andrzej, and Ashraf Mikhail. 2006. “European Regulatory Guidelines for Biosimilars.” Nephrology Dialysis Transplantation 21 (SUPPL. 5): 17–20. https://doi.org/10.1093/ndt/gfl477.
45. Wu, Ching Wen, Hsiao Chun Liu, Yung Luen Yu, Yu Ting Hung, Chyou Wei Wei, and Giou Teng Yiang. 2017. “Combined Treatment with Vitamin C and Methotrexate Inhibits Triple-Negative Breast Cancer Cell Growth by Increasing H2O2 Accumulation and Activating Caspase-3 and P38 Pathways.” Oncology Reports 37 (4): 2177–84. https://doi.org/10.3892/or.2017.5439.
46. Yang, Muyang, Lixia Yu, Ruiwei Guo, Anjie Dong, Cunguo Lin, and Jianhua Zhang. 2018. “A Modular Coassembly Approach to All-in-One Multifunctional Nanoplatform for Synergistic Codelivery of Doxorubicin and Curcumin.” Nanomaterials 8 (3): 1–18. https://doi.org/10.3390/nano8030167.
47. Yuan, Lie, Yongqing Cai, Liang Zhang, Sijia Liu, Pan Li, and Xiaoli Li. 2022. “Promoting Apoptosis, a Promising Way to Treat Breast Cancer With Natural Products: A Comprehensive Review.” Frontiers in Pharmacology 12 (January): 1–45. https://doi.org/10.3389/fphar.2021.801662.
48. Zafar, Ameeduzzafar, Nabil K. Alruwaili, Dibya Sundar Panda, Syed Sarim Imam, Khalid Saad Alharbi, Muhammad Afzal, Khaled Shalaby, Imran Kazmi, and Sultan Alshehri. 2021. “Potential of Natural Bioactive Compounds in Management of Diabetes: Review of Preclinical and Clinical Evidence.” Current Pharmacology Reports 7 (3): 107–22. https://doi.org/10.1007/s40495-021-00255-8.
49. Zhang, Lu, Zhaomin Lin, Yuan Chen, Dongfang Gao, Peng Wang, Yuxing Lin, Yongmei Wang, Fang Wang, Ying Han, and Huiqing Yuan. 2022. “Co-Delivery of Docetaxel and Resveratrol by Liposomes Synergistically Boosts Antitumor Efficiency against Prostate Cancer.” European Journal of Pharmaceutical Sciences 174 (April): 106199. https://doi.org/10.1016/j.ejps.2022.106199.