https://scholars.lib.ntu.edu.tw/handle/123456789/623895
標題: | pH-Responsive, two-in-one doxorubicin and Bcl-2 siRNA-loaded micelleplexes for triple-negative breast cancer therapy | 作者: | Lu H.-H. Liu H.W. Dinh T.K. Huang C.-H. Huang H.-C. Tseng Y.-C. Ku M.-H. Wang F.-S. Chen Y. Peng C.-H. |
公開日期: | 2022 | 來源出版物: | Polymer Chemistry | 摘要: | The combination of chemotherapy and gene therapy is a versatile strategy for treating multi-drug-resistant cancer. Accordingly, we developed a pH-responsive triblock copolymeric carrier for delivering chemotherapeutic and genetic drugs simultaneously. We synthesized a series of block and random copolymers with the same monomer composition, namely poly(ethylene glycol)-b-poly(2-(dimethylamino)ethyl methacrylate)-b-poly(2-(diisopropylamino)ethyl methacrylate) (PEG-b-PDMAEMA-b-PDPA) and poly(ethylene glycol)-b-poly[(2-(dimethylamino)ethyl methacrylate)-r-(2-(diisopropylamino)ethyl methacrylate)] (PEG-b-(PDMAEMA-r-PDPA)), by using atom transfer radical polymerization (ATRP) and then used them to encapsulate and release doxorubicin (Dox) and Bcl-2 siRNA. Compared with the random copolymers, the block copolymers exhibited a higher Dox-loading efficiency and Dox-loading capacity and higher Bcl-2 siRNA condensation efficiency. The siRNA condensation efficiency could be increased by increasing the length of the PDMAEMA segment in either the block copolymers or random copolymers. PEG-b-PDMAEMA-b-PDPA encapsulated Dox and Bcl-2 siRNA to form Dox/Bcl-2 siRNA-loaded micelleplexes with 87% and 90% loading efficiency, respectively. Changing the pH value from 7.4 to 5.0 engendered a burst release of Dox and Bcl-2 siRNA from the Dox/Bcl-2 siRNA-loaded micelleplexes, thus enhancing the cumulative release efficiency of Dox from 24% to 69% and that of Bcl-2 siRNA from 15% to 59% within 24 h. Our in vitro study revealed that the Dox/Bcl-2 siRNA-loaded micelleplexes downregulated Bcl-2 mRNA expression (51% expression) and further inhibited antiapoptotic mechanisms to sensitize drug-resistant triple-negative breast cancer (TNBC) cells to Dox (36% cell viability); this thus demonstrates the benefits of combining chemotherapy and gene therapy. ? 2022 The Royal Society of Chemistry. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85138832730&doi=10.1039%2fd2py00246a&partnerID=40&md5=d2b70ebf58e03096fb4a3c192f9fb731 https://scholars.lib.ntu.edu.tw/handle/123456789/623895 |
DOI: | 10.1039/d2py00246a | SDG/關鍵字: | Atom transfer radical polymerization;Block copolymers;Chemotherapy;Condensation;Controlled drug delivery;Diseases;Efficiency;Ethylene glycol;Gene therapy;Polyethylene oxides;Polyols;Targeted drug delivery;Block co polymers;Doxorubicin;Ethylmethacrylate;PDMAEMA;PH-responsive;Poly ethylene glycols;Poly((2dimethylamino)ethyl methacrylate);Poly(ethylene glycol);Random copolymer;Triple-negative breast cancers;Polyethylene glycols |
顯示於: | 化學系 |
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