Polymeric nanoparticles and fluoropyrimidine platforms in targeted cancer therapy

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Authors

  • Pritam I. Pawara R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India
  • Md. Mojeeb G. Khan R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India
  • Atul A. Shirkhedkar R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra, India
  • Harshada P. Pawara DCS’s ARA College of Pharmacy, Nagaon, Dhule, Maharashtra, India

Abstract

Targeted cancer therapy has been significantly advanced by the development of polymeric nanoparticles and novel fluoropyrimidine platforms. Polymeric carriers offer controlled release, biocompatibility, and surface modification capabilities that enhance tumor-specific drug delivery while minimizing systemic toxicity. Fluoropyrimidines such as 5-fluorouracil (5-FU) have long been central to chemotherapeutic regimens, yet their therapeutic window is often limited by metabolic instability and resistance. Recent innovations in nanoscale formulation, including the synthesis of polymer-conjugated fluoropyrimidines like CF10, demonstrate improved pharmacokinetics, tumor uptake, and anti-proliferative efficacy in preclinical models. This review summarizes current advancements in polymeric nanocarriers for delivering fluoropyrimidine derivatives, discusses formulation strategies to overcome drug resistance, and highlights translational applications in gastrointestinal and gynecologic malignancies. Together, these approaches represent a promising direction in the design of next-generation chemotherapeutic systems.

Keywords:

Polymeric nanoparticles, Fluoropyrimidines, Targeted cancer therapy, 5-fluorouracil (5-FU), Drug resistance, Nanocarriers

DOI

https://doi.org/10.70604/jmtbas.v2i2.80

References

1. Sethy C, Kundu CN. 5-Fluorouracil (5-FU) resistance and the new strategy to enhance the sensitivity against cancer: Implication of DNA repair inhibition. Biomedicine & Pharmacotherapy [Internet]. 2021 May 1 [cited 2025 Jul 8];137:111285. Available from: https://www.sciencedirect.com/science/article/pii/S0753332221000706

2. Wei QY, Xu YM, Lau ATY. Recent Progress of Nanocarrier-Based Therapy for Solid Malignancies. Cancers [Internet]. 2020 Oct [cited 2025 Jul 8];12(10):2783. Available from: https://www.mdpi.com/2072-6694/12/10/2783

3. Vagena IA, Malapani C, Gatou MA, Lagopati N, Pavlatou EA. Enhancement of EPR Effect for Passive Tumor Targeting: Current Status and Future Perspectives. Applied Sciences [Internet]. 2025 Jan [cited 2025 Jul 8];15(6):3189. Available from: https://www.mdpi.com/2076-3417/15/6/3189

4. Prajapati A, Rangra S, Patil R, Desai N, Jyothi VGSS, Salave S, et al. Receptor-Targeted Nanomedicine for Cancer Therapy. Receptors [Internet]. 2024 Sep [cited 2025 Jul 8];3(3):323–61. Available from: https://www.mdpi.com/2813-2564/3/3/16

5. Ghazal H, Waqar A, Yaseen F, Shahid M, Sultana M, Tariq M, et al. Role of nanoparticles in enhancing chemotherapy efficacy for cancer treatment. Next Materials [Internet]. 2024 Jan 1 [cited 2025 Jul 8];2:100128. Available from: https://www.sciencedirect.com/science/article/pii/S294982282400025X

6. Huddleston C, Mani C, Sah N, Courtney E, Reese K, Stroever S, et al. Evaluating Efficacy of Cervical HPV-HR DNA Testing as Alternative to PET/CT Imaging for Posttreatment Cancer Surveillance: Retrospective Proof-of-Concept Study. Cancer Epidemiology, Biomarkers & Prevention [Internet]. 2025 Jun 4 [cited 2025 Jul 8];OF1–5. Available from: https://doi.org/10.1158/1055-9965.EPI-24-1828

7. Okechukwu CC, Ma X, Sah N, Mani C, Palle K, Gmeiner WH. Enhanced Therapeutic Efficacy of the Nanoscale Fluoropyrimidine Polymer CF10 in a Rat Colorectal Cancer Liver Metastasis Model. Cancers [Internet]. 2024 Jan [cited 2025 Jul 8];16(7):1360. Available from: https://www.mdpi.com/2072-6694/16/7/1360

8. Sah N, Luna P, Mani C, Gmeiner W, Palle K. Abstract 6178: A novel second-generation nano-fluoropyrimidine to treat metastatic colorectal cancer and overcome 5-fluorouracil resistance. Cancer Research [Internet]. 2023 Apr 4 [cited 2025 Jul 8];83(7_Supplement):6178. Available from: https://doi.org/10.1158/1538-7445.AM2023-6178

9. Sah N, Luna P, Mani C, Gmeiner W, Palle K. A Novel Fluoropyrimidine Drug to Treat Recalcitrant Colorectal Cancer. The Journal of Pharmacology and Experimental Therapeutics [Internet]. 2023 Jun 1 [cited 2025 Jul 8];385:441. Available from: https://www.sciencedirect.com/science/article/pii/S0022356524168796

10. Pridgen EM, Alexis F, Farokhzad OC. Polymeric Nanoparticle Technologies for Oral Drug Delivery. Clinical Gastroenterology and Hepatology [Internet]. 2014 Oct 1 [cited 2025 Jul 8];12(10):1605–10. Available from: https://www.cghjournal.org/article/S1542-3565(14)00923-9/fulltext

11. Calzoni E, Cesaretti A, Polchi A, Di Michele A, Tancini B, Emiliani C. Biocompatible Polymer Nanoparticles for Drug Delivery Applications in Cancer and Neurodegenerative Disorder Therapies. J Funct Biomater [Internet]. 2019 Jan 8 [cited 2025 Jul 8];10(1):4. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463038/

12. Suk JS, Xu Q, Kim N, Hanes J, Ensign LM. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv Drug Deliv Rev [Internet]. 2016 Apr 1 [cited 2025 Jul 8];99(Pt A):28–51. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4798869/

13. Yao Y, Zhou Y, Liu L, Xu Y, Chen Q, Wang Y, et al. Nanoparticle-Based Drug Delivery in Cancer Therapy and Its Role in Overcoming Drug Resistance. Front Mol Biosci [Internet]. 2020 Aug 20 [cited 2025 Jul 8];7:193. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468194/

14. Ying N, Lin X, Xie M, Zeng D. Effect of surface ligand modification on the properties of anti-tumor nanocarrier. Colloids and Surfaces B: Biointerfaces [Internet]. 2022 Dec 1 [cited 2025 Jul 8];220:112944. Available from: https://www.sciencedirect.com/science/article/pii/S0927776522006282

15. Shakeri-Zadeh A, Rezaeyan A, Sarikhani A, Ghaffari H, Samadian H, Khademi S, et al. Folate receptor-targeted nanoprobes for molecular imaging of cancer: Friend or foe? Nano Today [Internet]. 2021 Aug 1 [cited 2025 Jul 8];39:101173. Available from: https://www.sciencedirect.com/science/article/pii/S1748013221000980

16. Necela BM, Crozier JA, Andorfer CA, Lewis-Tuffin L, Kachergus JM, Geiger XJ, et al. Folate Receptor-α (FOLR1) Expression and Function in Triple Negative Tumors. PLOS ONE [Internet]. 2015 Mar 27 [cited 2025 Jul 8];10(3):e0122209. Available from: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0122209

17. Bazak R, Houri M, Achy SE, Kamel S, Refaat T. Cancer active targeting by nanoparticles: a comprehensive review of literature. J Cancer Res Clin Oncol [Internet]. 2015 May [cited 2025 Jul 8];141(5):769–84. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710367/

18. Pridgen EM, Alexis F, Farokhzad OC. Polymeric Nanoparticle Technologies for Oral Drug Delivery. Clinical Gastroenterology and Hepatology [Internet]. 2014 Oct 1 [cited 2025 Jul 8];12(10):1605–10. Available from: https://www.cghjournal.org/article/S1542-3565(14)00923-9/fulltext

19. Zhang YQ, Guo RR, Chen YH, Li TC, Du WZ, Xiang RW, et al. Ionizable drug delivery systems for efficient and selective gene therapy. Military Medical Research [Internet]. 2023 Feb 27 [cited 2025 Jul 8];10(1):9. Available from: https://doi.org/10.1186/s40779-023-00445-z

20. Liu Y, Chen L, Shi Q, Zhao Q, Ma H. Tumor Microenvironment–Responsive Polypeptide Nanogels for Controlled Antitumor Drug Delivery. Front Pharmacol [Internet]. 2021 Oct 27 [cited 2025 Jul 8];12:748102. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8578677/

21. Sun R, Chen Y, Pei Y, Wang W, Zhu Z, Zheng Z, et al. The drug release of PLGA-based nanoparticles and their application in treatment of gastrointestinal cancers. Heliyon [Internet]. 2024 Sep 30 [cited 2025 Jul 8];10(18):e38165. Available from: https://www.sciencedirect.com/science/article/pii/S2405844024141965

22. Hoang Thi TT, Pilkington EH, Nguyen DH, Lee JS, Park KD, Truong NP. The Importance of Poly(ethylene glycol) Alternatives for Overcoming PEG Immunogenicity in Drug Delivery and Bioconjugation. Polymers [Internet]. 2020 Feb [cited 2025 Jul 8];12(2):298. Available from: https://www.mdpi.com/2073-4360/12/2/298

23. Grewal AK, Salar RK. Chitosan nanoparticle delivery systems: An effective approach to enhancing efficacy and safety of anticancer drugs. Nano TransMed [Internet]. 2024 Dec 1 [cited 2025 Jul 8];3:100040. Available from: https://www.sciencedirect.com/science/article/pii/S2790676024000116

24. Fu X, Hosta-Rigau L, Chandrawati R, Cui J. Multi-Stimuli-Responsive Polymer Particles, Films, and Hydrogels for Drug Delivery. Chem [Internet]. 2018 Sep 13 [cited 2025 Jul 8];4(9):2084–107. Available from: https://www.sciencedirect.com/science/article/pii/S2451929418303127

25. Schumacher TJ, Sah N, Palle K, Rumbley J, Mereddy VR. Synthesis and biological evaluation of benzofuran piperazine derivatives as potential anticancer agents. Bioorganic & Medicinal Chemistry Letters [Internet]. 2023 Sep 1 [cited 2025 Jul 8];93:129425. Available from: https://www.sciencedirect.com/science/article/pii/S0960894X23003037

26. Sun L, Li Z, Lan J, Wu Y, Zhang T, Ding Y. Better together: nanoscale co-delivery systems of therapeutic agents for high-performance cancer therapy. Front Pharmacol [Internet]. 2024 May 20 [cited 2025 Jul 8];15. Available from: https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1389922/full

27. Cox J, Weinman S. Mechanisms of doxorubicin resistance in hepatocellular carcinoma. Hepat Oncol [Internet]. 2016 Jan [cited 2025 Jul 8];3(1):57–9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792121/

28. Arvejeh PM, Chermahini FA, Marincola F, Taheri F, Mirzaei SA, Alizadeh A, et al. A novel approach for the co-delivery of 5-fluorouracil and everolimus for breast cancer combination therapy: stimuli-responsive chitosan hydrogel embedded with mesoporous silica nanoparticles. J Transl Med. 2025 Mar 31;23(1):382.

29. Young C, Schluep T, Hwang J, Eliasof S. CRLX101 (formerly IT-101)–A Novel Nanopharmaceutical of Camptothecin in Clinical Development. Curr Bioact Compd [Internet]. 2011 Mar [cited 2025 Jul 8];7(1):8–14. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182091/

30. Ma P, Mumper RJ. Paclitaxel Nano-Delivery Systems: A Comprehensive Review. J Nanomed Nanotechnol [Internet]. 2013 Feb 18 [cited 2025 Jul 8];4(2):1000164. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3806207/

31. Sadat SMA, Jahan ST, Haddadi A. Effects of Size and Surface Charge of Polymeric Nanoparticles on in Vitro and in Vivo Applications. Journal of Biomaterials and Nanobiotechnology [Internet]. 2016 Mar 31 [cited 2025 Jul 8];7(2):91–108. Available from: https://www.scirp.org/journal/paperinformation?paperid=65756

32. Al-Sahlawi F, Alabdali AYM, Chinnappan S, Al-Samydai A, Maki MAA. Polymer-based nanoparticles in targeted cancer therapy: a review. J App Pharm Sci [Internet]. 2024 Sep 5 [cited 2025 Jul 8];14,(9):057–68. Available from: https://japsonline.com/abstract.php?article_id=4292&sts=2

33. Maslarinou A, Manolopoulos VG, Ragia G. Pharmacogenomic-guided dosing of fluoropyrimidines beyond DPYD: time for a polygenic algorithm? Front Pharmacol [Internet]. 2023 May 15 [cited 2025 Jul 8];14. Available from: https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1184523/full

34. Casale J, Patel P. Fluorouracil. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 [cited 2025 Jul 8]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK549808/

35. Entezar-Almahdi E, Mohammadi-Samani S, Tayebi L, Farjadian F. Recent Advances in Designing 5-Fluorouracil Delivery Systems: A Stepping Stone in the Safe Treatment of Colorectal Cancer. Int J Nanomedicine [Internet]. 2020 Jul 30 [cited 2025 Jul 8];15:5445–58. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398750/

36. Haggag YA, Osman MA, El-Gizawy SA, Goda AE, Shamloula MM, Faheem AM, et al. Polymeric nano-encapsulation of 5-fluorouracil enhances anti-cancer activity and ameliorates side effects in solid Ehrlich Carcinoma-bearing mice. Biomedicine & Pharmacotherapy [Internet]. 2018 Sep 1 [cited 2025 Jul 8];105:215–24. Available from: https://www.sciencedirect.com/science/article/pii/S0753332218322662

37. Liu Y, Si L, Jiang Y, Jiang S, Zhang X, Li S, et al. Design of pH-Responsive Nanomaterials Based on the Tumor Microenvironment. IJN [Internet]. 2025 Jan 18 [cited 2025 Jul 8];20:705–21. Available from: https://www.dovepress.com/design-of-ph-responsive-nanomaterials-based-on-the-tumor-microenvironm-peer-reviewed-fulltext-article-IJN

38. Anjum S, Naseer F, Ahmad T, Jahan F, Qadir H, Gul R, et al. Publisher Correction: Enhancing therapeutic efficacy: sustained delivery of 5-fluorouracil (5-FU) via thiolated chitosan nanoparticles targeting CD44 in triple-negative breast cancer. Sci Rep. 2024 Jul 25;14(1):17125.

39. Nabil G, Alzhrani R, Alsaab HO, Atef M, Sau S, Iyer AK, et al. CD44 Targeted Nanomaterials for Treatment of Triple-Negative Breast Cancer. Cancers (Basel) [Internet]. 2021 Feb 20 [cited 2025 Jul 8];13(4):898. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924562/

40. Chandran SP, Natarajan SB, Chandraseharan S, Mohd Shahimi MSB. Nano drug delivery strategy of 5-fluorouracil for the treatment of colorectal cancer. Journal of Cancer Research and Practice [Internet]. 2017 Jun 1 [cited 2025 Jul 8];4(2):45–8. Available from: https://www.sciencedirect.com/science/article/pii/S2311300616301847

41. Hani U, Mahammed N, Reshma T, Talath S, Wali AF, Aljasser A, et al. Enhanced colon-targeted drug delivery through development of 5-fluorouracil-loaded cross-linked mastic gum nanoparticles. Sci Rep [Internet]. 2025 May 26 [cited 2025 Jul 8];15(1):18355. Available from: https://www.nature.com/articles/s41598-025-03533-3

42. Ahmadi E, Sadrjavadi K, Mohammadi G, Fattahi A. De-Esterified Tragacanth Microspheres Loaded into Eudragit S-100 Coated Capsules for Colon-Targeted Delivery. Iran J Pharm Res [Internet]. 2018 [cited 2025 Jul 8];17(2):470–9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985165/

43. Wathoni N, Nguyen AN, Rusdin A, Umar AK, Mohammed AFA, Motoyama K, et al. Enteric-Coated Strategies in Colorectal Cancer Nanoparticle Drug Delivery System. Drug Des Devel Ther [Internet]. 2020 Oct 21 [cited 2025 Jul 8];14:4387–405. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585804/

44. Omy TR, Sah N, Reedy M, Acharya G, Palle K. Abstract 3090: miRNA-221-5p-mediated epigenetic regulation promotes chemoresistance and offers therapeutic potential in ovarian cancer. Cancer Research [Internet]. 2025 Apr 21 [cited 2025 Jul 8];85(8_Supplement_1):3090. Available from: https://doi.org/10.1158/1538-7445.AM2025-3090

45. Xiao B, Ma L, Merlin D. Nanoparticle-mediated co-delivery of chemotherapeutic agent and siRNA for combination cancer therapy. Expert Opin Drug Deliv [Internet]. 2017 Jan [cited 2025 Jul 8];14(1):65–73. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5531052/

46. Ding L, Lan Z, Xiong X, Ao H, Feng Y, Gu H, et al. The Dual Role of MicroRNAs in Colorectal Cancer Progression. Int J Mol Sci [Internet]. 2018 Sep 17 [cited 2025 Jul 8];19(9):2791. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164944/

47. Arvejeh PM, Chermahini FA, Marincola F, Taheri F, Mirzaei SA, Alizadeh A, et al. A novel approach for the co-delivery of 5-fluorouracil and everolimus for breast cancer combination therapy: stimuli-responsive chitosan hydrogel embedded with mesoporous silica nanoparticles. Journal of Translational Medicine [Internet]. 2025 Mar 31 [cited 2025 Jul 8];23(1):382. Available from: https://doi.org/10.1186/s12967-025-06396-4

48. Valencia-Lazcano AA, Hassan D, Pourmadadi M, Shamsabadipour A, Behzadmehr R, Rahdar A, et al. 5-Fluorouracil nano-delivery systems as a cutting-edge for cancer therapy. Eur J Med Chem. 2023 Jan 15;246:114995.

49. Saeed BQ, Qalaji MR, Akbar N, Siddiqui R, Roberta C, Manzoor S, et al. Evaluation of nanoparticles with 5-fluorouracil and chloroquine on Acanthamoeba castellanii activity. Molecular and Biochemical Parasitology [Internet]. 2022 Jul 1 [cited 2025 Jul 8];250:111492. Available from: https://www.sciencedirect.com/science/article/pii/S0166685122000469

50. Nguyen HM, Sah N, Humphrey MRM, Rabkin SD, Saha D. Growth, Purification, and Titration of Oncolytic Herpes Simplex Virus. J Vis Exp [Internet]. 2021 May 13 [cited 2025 Jul 8];(171):10.3791/62677. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447238/

51. Wang H, Borlongan M, Hemminki A, Basnet S, Sah N, Kaufman HL, et al. Viral Vectors Expressing Interleukin 2 for Cancer Immunotherapy. Hum Gene Ther. 2023 Sep;34(17–18):878–95.

52. Raj M, Meena A, Seth R, Mathur A, Luqman S. An update on nanoformulations with FDA approved drugs for female reproductive cancer. Journal of Microencapsulation [Internet]. 2025 Apr 3 [cited 2025 Jul 8];42(3):266–99. Available from: https://doi.org/10.1080/02652048.2025.2474457

53. Anjum S, Naseer F, Ahmad T, Jahan F, Qadir H, Gul R, et al. Enhancing therapeutic efficacy: sustained delivery of 5-fluorouracil (5-FU) via thiolated chitosan nanoparticles targeting CD44 in triple-negative breast cancer. Sci Rep [Internet]. 2024 May 19 [cited 2025 Jul 8];14(1):11431. Available from: https://www.nature.com/articles/s41598-024-55900-1

54. Mestiri S, Sami A, Sah N, El-Ella DMA, Khatoon S, Shafique K, et al. Cellular plasticity and non-small cell lung cancer: role of T and NK cell immune evasion and acquisition of resistance to immunotherapies. Cancer Metastasis Rev. 2025 Jan 25;44(1):27.

55. Liu X, Tang I, Wainberg ZA, Meng H. Safety Considerations of Cancer Nanomedicine – A key step towards translation. Small [Internet]. 2020 Sep [cited 2025 Jul 8];16(36):e2000673. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486239/

Harshada P. Pawara

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2025-08-28
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Pawara, P. I., Khan, M. M. G., Shirkhedkar, A. A., & Pawara, H. P. (2025). Polymeric nanoparticles and fluoropyrimidine platforms in targeted cancer therapy: `. Journal of Modern Techniques in Biology and Allied Sciences, 2(2), 19-26. https://doi.org/10.70604/jmtbas.v2i2.80

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Pawara, P. I., Khan, M. M. G., Shirkhedkar, A. A., & Pawara, H. P. (2025). Polymeric nanoparticles and fluoropyrimidine platforms in targeted cancer therapy: `. Journal of Modern Techniques in Biology and Allied Sciences, 2(2), 19-26. https://doi.org/10.70604/jmtbas.v2i2.80