2. Academic Validation
  3. Chemically Cross-Linked Nanocapsules from Terpolymers of Polyethylene Glycol-Polylactide with Cationic Pendent Groups for Pgp-siRNA and Doxorubicin Codelivery in Overcoming Multidrug Resistance in Breast Cancer

Chemically Cross-Linked Nanocapsules from Terpolymers of Polyethylene Glycol-Polylactide with Cationic Pendent Groups for Pgp-siRNA and Doxorubicin Codelivery in Overcoming Multidrug Resistance in Breast Cancer

  • Mol Pharm. 2025 Nov 28. doi: 10.1021/acs.molpharmaceut.4c00600.
Zheng-Ian Lin 1 2,  Tzu-Hsien Tsai 3,  Li-Hsien Wu 4,  Chien-Hou Lu 5,  Chih-Yuan Hsu 1,  Haiqing Liang 6,  Hsin-Yu Lin 1,  Yi-Ping Fang 7 8 9,  Wing-Cheung Law 10,  Cheng-Hsi Chang 3,  Hau-En Liou 3,  Chengbin Yang 6 11,  Pei-Wen Cheng 2 12,  Che-Hsin Lee 4 13 14 15 16,  Chih-Kuang Chen 1
Affiliations

Affiliations

  • 1 Polymeric Biomaterials Laboratory, Department of Materials and Optoelectronic Science, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan.
  • 2 Department of Medical Education and Research, Kaohsiung Veterans General Hospital Kaohsiung, Kaohsiung 81362, Taiwan.
  • 3 Division of Cardiology and Department of Internal Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi 60002, Taiwan.
  • 4 Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan.
  • 5 Department of Fiber and Composite Materials, Feng Chia University, Taichung 40724, Taiwan.
  • 6 Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong 518060, P. R. China.
  • 7 School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
  • 8 Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan.
  • 9 Regenerative Medical and Cell Therapy Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
  • 10 Department of Industrial and Systems Engineering, The Hong Kong Polytechnic University, Hung Hom, Hong Kong 999077, P. R. China.
  • 11 The Shenzhen Key Laboratory of Metabolism and Cardiovascular Homeostasis, Shenzhen University, Shenzhen 518060, China.
  • 12 Department of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan.
  • 13 Aerosol Science Research Center, National Sun Yat-sen University, Kaohsiung 80424, Taiwan.
  • 14 College of Semiconductor and Advanced Technology Research, National Sun Yat-sen University, Kaohsiung 80424, Taiwan.
  • 15 Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
  • 16 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404327, Taiwan.
PMID: 41314773 DOI: 10.1021/acs.molpharmaceut.4c00600
Abstract

Cancer remains one of the leading causes of mortality worldwide. Among current treatment strategies, chemotherapy continues to play a central role; however, its therapeutic efficacy is markedly compromised by the development of multidrug resistance (MDR) in Cancer cells. To address this challenge, a new triblock copolymer, poly(ethylene glycol)-b-poly(lactide)-b-poly(cationic polylactide) (PEG-b-PLA-b-CPLA), was first synthesized and converted into biodegradable charged nanocapsules (BCNCs) without the use of Surfactants or additives via our developed nanoemulsion interfacial cross-linking technique. With favorable biodegradability, BCNCs exhibit the ability to coload both hydrophobic drugs and hydrophilic genes. Compared with Other drug/gene carriers, they feature controllable charge and surface poly(ethylene glycol) (PEG) density, high colloidal stability, and sequential release of the loaded genes and drugs. When loaded with a hydrophobic Anticancer drug, dehydrochlorination doxorubicin (Dox), and a hydrophilic P-glycoprotein (Pgp) silencing gene (Pgp-siRNA), the resulting Pgp-siRNA/Dox-coloaded BCNCs successfully demonstrated the ability to overcome MDR in MCF-7/ADR cells, due to enhanced cellular uptake, Pgp silencing efficiency, and effective endosomal/lysosomal escape of the loaded therapeutics.

Keywords

cancer; drug/gene coloading; multidrug resistance; nanocapsules; polylactide.

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