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Volume 19, Issue 2 (Iranian Journal of Breast Diseases 2026)                   ijbd 2026, 19(2): 53-76 | Back to browse issues page

Ethics code: IR.IAU.TABRIZ.REC.1401.265


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Yaghoubi H, Zaefizadeh M. Targeted co-delivery of paclitaxel and siRNA using PLA-Chitosan-PEG-Folic acid copolymer nanoparticles for treatment of MCF-7 breast cancer cells. ijbd 2026; 19 (2) :53-76
URL: http://ijbd.ir/article-1-1220-en.html
1- Department of Biology, Ard.C., Islamic Azad University, Ardabil, Iran , yaghoubi_h@iau.ac.ir
2- Traditional Medicine and Hydrotherapy Research Center, Ardabil University Of Medical Sciences, Ardabil, Iran
Abstract:   (777 Views)

Introduction: Nanotechnology addresses the challenge of targeted delivery of drugs and nucleic acids to cancer cells by designing smart delivery systems. This approach enables improved precision and efficiency in the delivery of therapeutic agents. This study focuses on the design and evaluation of a folic acid (FA)-functionalized, PLA/Chitosan/PEG-based multifunctional nanocarrier with tumor-targeting capability and synergistic co-delivery of paclitaxel (PTX) and siRNA to breast cancer cells (MCF-7), aiming to enhance selective uptake and therapeutic efficiency compared to conventional delivery systems.
Methods: PCPF nanoparticles were synthesized and co-loaded with PTX and Survivin-targeting siRNA. FTIR and DLS characterized physicochemical properties. Cargo release was evaluated at different pH values, while cytotoxicity and apoptosis were assessed in MCF-7 and MCF-10A cells using MTT and Annexin V/PI assays, respectively.
Results: FTIR confirmed successful PCPF nanoparticle synthesis. Particle size increased from 162 ± 6 nm to 256 ± 11 nm after PTX/siRNA loading, while zeta potential remained mainly negative. Nanocapsules exhibited pH-responsive sustained release, with greater cargo release at pH 5.0. Cytotoxicity studies demonstrated enhanced selectivity for MCF-7 cells, with PCPF/PTX/siRNA inducing the highest apoptosis, whereas free PTX caused the greatest necrosis.
Conclusion: Folic acid-targeted PCPF nanoparticles enhanced PTX/siRNA co-delivery, promoting selective cytotoxicity, apoptosis, and improved anticancer efficacy.

Full-Text [PDF 5079 kb]   (282 Downloads)    
Type of Study: Research | Subject: molecular cell
Received: 2025/11/8 | Accepted: 2026/06/3 | Published: 2026/07/26

References
1. Ahmad A. Breast cancer statistics: recent trends. Breast cancer metastasis and drug resistance: challenges and progress. 2019:1-7. doi: org/10.1007/978-3-030-20301-6-1 [DOI:10.1007/978-3-030-20301-6_1] [PMID]
2. Bourang S, Noruzpour M, Jahanbakhsh Godekahriz S, Ebrahimi HA, Amani A, Asghari Zakaria R, et al. Application of nanoparticles in breast cancer treatment: a systematic review. Naunyn-Schmiedeberg's Archives of Pharmacology. 2024;397(9):6459-505. doi:org/10.1007/s00210-024-03082-y. [DOI:10.1007/s00210-024-03082-y] [PMID]
3. Yahya EB, Alqadhi AM. Recent trends in cancer therapy: A review on the current state of gene delivery. Life Sciences. 2021;296:124-138. doi: org/10.1016/j.lfs.2021.119087. [DOI:10.1016/j.lfs.2021.119087] [PMID]
4. Bahrami B, Hojjat-Farsangi M, Mohammadi H, Anvari E, Ghalamfarsa G, Yousefi M, et al. Nanoparticles and targeted drug delivery in cancer therapy. Immunology Letters. 2017;190:64-83. doi: org/10.1016/j.imlet.2017.07.015. [DOI:10.1016/j.imlet.2017.07.015] [PMID]
5. Liu C, Zhang L, Zhu W, Guo R, Sun H, Chen X, et al. Barriers and strategies of cationic liposomes for cancer gene therapy. Molecular Therapy Methods & Clinical Development. 2020;18:751-64. doi: org/10.1016/j.omtm.2020.07.015. [DOI:10.1016/j.omtm.2020.07.015] [PMID] [PMCID]
6. Mosleh-Shirazi S, Abbasi M, Reza Moaddeli M, Vaez A, Shafiee M, Kasaee SR, et al. Nanotechnology advances in the detection and treatment of cancer: an overview. Nanotheranostics. 2022;6(4):400. doi:org/10.7150/ntno.74613. [DOI:10.7150/ntno.74613] [PMID] [PMCID]
7. Xu X, Liu C, Wang Y, Koivisto O, Zhou J, Shu Y, et al. Nanotechnology-based delivery of CRISPR/Cas9 for cancer treatment. Advanced drug delivery reviews. 2021;176:1-31. doi: org/10.1016/j.addr.2021.113891 [DOI:10.1016/j.addr.2021.113891] [PMID]
8. Mohajeri S, Yaghoubi H, Bourang S, Noruzpour M. Multifunctional magnetic nanocapsules for dual delivery of siRNA and chemotherapy to MCF-7 cells (Breast cancer cells). Naunyn-Schmiedeberg's Archives of Pharmacology. 2025:1-23. doi: org/10.1007/s00210-025-04381-8. [DOI:10.1007/s00210-025-04381-8] [PMID]
9. Dastgerdi NK, Dastgerdi NK, Bayraktutan H, Costabile G, Atyabi F, Dinarvand R, et al. Enhancing siRNA cancer therapy: Multifaceted strategies with lipid and polymer-based carrier systems. International Journal of Pharmaceutics. 2024:124-138. doi: org/10.1016/j.ijpharm.2024.124545. [DOI:10.1016/j.ijpharm.2024.124545] [PMID]
10. Zenjanab MK, Alimohammadvand S, Doustmihan A, Kianian S, Oskouei BS, Mazloomi M, et al. Paclitaxel for breast cancer therapy: a review on effective drug combination modalities and nano drug delivery platforms. Journal of Drug Delivery Science and Technology. 2024;95:105-126. doi: org/10.1016/j.jddst.2024.105567 [DOI:10.1016/j.jddst.2024.105567]
11. Czabotar PE, García-Sáez AJ. Mechanisms of BCL-2 family proteins in mitochondrial apoptosis. Nature reviews Molecular cell biology. 2023;24(10):732-48. doi: org/10.1038/s41580-023-00629-4. [DOI:10.1038/s41580-023-00629-4] [PMID]
12. Sati P, Sharma E, Dhyani P, Attri DC, Rana R, Kiyekbayeva L, et al. Paclitaxel and its semi-synthetic derivatives: comprehensive insights into chemical structure, mechanisms of action, and anticancer properties. European journal of medical research. 2024;29(1): 90-124. doi: org/10.1186/s40001-024-01657-2. [DOI:10.1186/s40001-024-01657-2] [PMID] [PMCID]
13. Reshma P, Unnikrishnan B, Preethi G, Syama H, Archana M, Remya K, et al. Overcoming drug-resistance in lung cancer cells by paclitaxel loaded galactoxyloglucan nanoparticles. International journal of biological macromolecules. 2019;136:266-74. doi: org/10.1016/j.ijbiomac.2019.06.075. [DOI:10.1016/j.ijbiomac.2019.06.075] [PMID]
14. Abebe DG, Kandil R, Kraus T, Elsayed M, Merkel OM, Fujiwara T. Three‐layered biodegradable micelles prepared by two‐step self‐assembly of PLA‐PEI‐PLA and PLA‐PEG‐PLA triblock copolymers as efficient gene delivery system. Macromolecular bioscience. 2015;15(5):698-711. doi: org/10.1002/mabi. 201400488 [DOI:10.1002/mabi.201400488] [PMID]
15. Amani A, Kabiri T, Shafiee S, Hamidi A. Preparation and characterization of PLA-PEG-PLA/PEI/DNA nanoparticles for improvement of transfection efficiency and controlled release of DNA in gene delivery systems. Iranian journal of pharmaceutical research. 2019;18(1):125. doi: org/10.1016/j.jddst.2022.104016.
16. Mohajeri S, Dashti S, Noruzpour M, Bourang S, Yaghoubi H. Design and preparation of PLA-chitosan-PEG-glucose copolymer for combined delivery of Paclitaxel and siRNA. Discover Applied Sciences. 2025;7(8):801. doi: org/10.1007/s42452-025-07458-4. [DOI:10.1007/s42452-025-07458-4]
17. Mundel R, Thakur T, Chatterjee M. Emerging uses of PLA-PEG copolymer in cancer drug delivery. Biotech. 2022;12(2):41. doi:org/10.1007/s13205-021-03105-y. [DOI:10.1007/s13205-021-03105-y] [PMID] [PMCID]
18. Kesharwani P, Halwai K, Jha SK, Al Mughram MH, Almujri SS, Almalki WH, et al. Folate-engineered chitosan nanoparticles: next-generation anticancer nanocarriers. Molecular Cancer. 2024;2(1): 244. doi: org/10.1186/s12943-024-02163-z [DOI:10.1186/s12943-024-02163-z] [PMID] [PMCID]
19. Mohajeri S, Raei M, Bourang S, Noruzpour M, Yaghoubi H. Multifunctional Polyspermine-based Nanocapsules for Targeted Gene Delivery to Gastric Cancer Cells. BioNanoScience. 2025;15(4):544. doi: org/10.1007/s12668-025-02167-z [DOI:10.1007/s12668-025-02167-z]
20. Zou W, Liu C, Chen Z, Zhang N. Preparation and characterization of cationic PLA-PEG nanoparticles for delivery of plasmid DNA. Nanoscale research letters. 2009;4:982-92. doi: org/10.1007/s11671-009-9345-3. [DOI:10.1007/s11671-009-9345-3] [PMID] [PMCID]
21. Bourang S, Jahanbakhsh Godehkahriz S, Noruzpour M, Asghari Zakaria R, Granados-Principal S. Anticancer properties of copolymer nanoparticles loaded with Foeniculum vulgare derivatives in Hs578T and SUM159 cancer cell lines. Cancer Nanotechnology. 2025;16(1):1-28. doi: org/10.1186/s12645-025-00318-1 [DOI:10.1186/s12645-025-00318-1]
22. Noruzpour M, Zakaria RA, Zare N, Bourang S, Ebrahimi HA, Granados-Principal S. Delivery of Moringa oleifera extract via PLA-PEG-FA/chitosan-PLA NPs into breast cancer cell lines. BioNanoScience. 2025;15(2):287. doi: org/10.1007/s12668-025-01902-w [DOI:10.1007/s12668-025-01902-w]
23. Bourang S, Asadian S, Noruzpour M, Mansuryar A, Azizi S, Ebrahimi HA, et al. PLA-HA/Fe3O4 magnetic nanoparticles loaded with curcumin: physicochemical characterization and toxicity evaluation in HCT116 colorectal cancer cells. Discover Applied Sciences. 2024;6(4):186. doi: org/10.1007/s42452-024-05858-6. [DOI:10.1007/s42452-024-05858-6]
24. Paunovska K, Loughrey D, Dahlman JE. Drug delivery systems for RNA therapeutics. Nature Reviews Genetics. 2022;23(5):265-80. doi: org/10.1038/s41576-021-00439-4. [DOI:10.1038/s41576-021-00439-4] [PMID] [PMCID]
25. Mohajeri S, Yaghoubi H. siRNA-FAM and Paclitaxel delivery to MCF-7 cells via folic acid-PLA-Spermine-PEG-Fe3O4 nanoparticles. Nanomedicine Journal. 2026;13:1. doi: org/10.1007/s12033-025-01454-0.
26. Wu Y, Li X, Fu X, Huang X, Zhang S, Zhao N, et al. Innovative nanotechnology in drug delivery systems for advanced treatment of posterior segment ocular diseases. Advanced science. 2024;11(32):24-35. doi: org/10.1002/advs. 202403399. [DOI:10.1002/advs.202403399] [PMID] [PMCID]
27. Mansuryar A, Bourang S, Noruzpour M, Ebrahimi HA, Amani A, Granados-Principal S, et al. The effect of Fe3O4 biosynthesized through the green synthesis of Silybum marianum and HA in the targeted delivery of 5-Fluorouracil to HCT116 cell line. DARU Journal of Pharmaceutical Sciences. 2025;33(2):27. doi: org/10.1007/s40199-025-00568-9. [DOI:10.1007/s40199-025-00568-9] [PMID] [PMCID]
28. Noruzpuor M, Asghari Zakaria R, Zare N, Ebrahimi HA, Parsa H, Bourang S. Green synthesis of metal nanoparticles using aqueous extract of Moringa oleifera L. and investigating their antioxidant and antibacterial properties. Applied Chemistry Today. 2024;19(71):283-02. doi: org/10.61186/ijbd. 17.1.59. [DOI:10.61186/ijbd.17.1.59]
29. Bourang S, Jahanbakhsh Godehkahriz S, Asghari Zakaria R, Parsa H, Noruzpuor M. Green synthesis of iron oxide, copper, zinc oxide, and silver nanoparticles from aqueous extract of F. vulgare and evaluation of their structural and antimicrobial properties. Agricultural Biotechnology Journal. 2024;16(3):60-88. doi: org/10.1186/s12645-025-00318-1.
30. Noruzpuor M, Asghari Zakaria R, Zare N, Ebrahimi HA, Parsa H, Bourang S. Investigating the anticancer properties of the essential oil and aqueous extract of Moringa oleifera and its biosynthesized metal nanoparticles on MCF-7 and BT-549 cell lines. Iranian Journal of Breast Diseases. 2024;17(1):59-83. doi: org/10.61186/ijbd. 17.1.59. [DOI:10.61186/ijbd.17.1.59]
31. Hu Q, Li H, Wang L, Gu H, Fan C. DNA nanotechnology-enabled drug delivery systems. Chemical reviews. 2018;119(10):459-506. doi: org/10.1021/acs.chemrev.7b00663. [DOI:10.1021/acs.chemrev.7b00663] [PMID]
32. Creixell M, Peppas NA. Co-delivery of siRNA and therapeutic agents using nanocarriers to overcome cancer resistance. Nano today. 2012;7(4):367-79. doi:org/10.1016/j.nantod.2012.06.013. [DOI:10.1016/j.nantod.2012.06.013] [PMID] [PMCID]
33. Li M, Li S, Li Y, Li X, Yang G, Li M, et al. Cationic liposomes co-deliver chemotherapeutics and siRNA for the treatment of breast cancer. European Journal of Medicinal Chemistry. 2022;233:114-198. doi:org/10.1016/j.ejmech.2022.114198. [DOI:10.1016/j.ejmech.2022.114198] [PMID]
34. Moghadam ME, Sadeghi M, Mansouri-Torshizi H, Saidifar M. High cancer selectivity and improving drug release from mesoporous silica nanoparticles in the presence of human serum albumin in cisplatin, carboplatin, oxaliplatin, and oxalipalladium treatment. European Journal of Pharmaceutical Sciences. 2023;187:106-177. doi: org/10.1016/j.ejps.2023.106477. [DOI:10.1016/j.ejps.2023.106477] [PMID]
35. Kundu S, Feizi-Dehnayebi M, Akkoc S. Exploring the anticancer potential of novel benzimidazolium salts: synthesis, biological evaluation, DFT perspective, and docking simulation for inhibition of VEGFR2. Biochemical and Biophysical Research Communications. 2025:152-172. doi: org/10.1016/j.bbrc.2025.152472. [DOI:10.1016/j.bbrc.2025.152472] [PMID]
36. Kaloni D, Diepstraten ST, Strasser A, Kelly GL. BCL-2 protein family: attractive targets for cancer therapy. Apoptosis. 2023;28(1):20-38. doi: org/10.1007/s10495-022-01780-7. [DOI:10.1007/s10495-022-01780-7] [PMID] [PMCID]
37. Green DR. Caspase activation and inhibition. Cold Spring Harbor Perspectives in Biology. 2022;14(8): 41-90. doi: org/10.1101/cshperspect.a041020. [DOI:10.1101/cshperspect.a041020] [PMID] [PMCID]
38. Romani AM. Cisplatin in cancer treatment. Biochemical pharmacology. 2022;206:115-123. doi: org/10.1016/j.bcp.2022.115323. [DOI:10.1016/j.bcp.2022.115323] [PMID]
39. Ahmadi M, Valizadeh A, Bazavar M, Yousefi B. Investigating the role of quercetin in increasing the rate of cisplatin-induced apoptosis via the NF-κB pathway in MG-63 cancer cells. Drug research. 2022;72(07):385-389. doi: org/10.1055/a-1842-7424. [DOI:10.1055/a-1842-7424] [PMID]

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