期刊
BIOMATERIALS
卷 35, 期 7, 页码 2322-2335出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2013.11.039
关键词
Star-branched copolymer; Polylactic acid; Polydimethylaminoethyl methacrylate; miR-21; Co-delivery; Synergistic effects
资金
- National Nature Science Foundation of China [51073118, 51103107, 81172406]
- Program for New Century Excellent Talents in Universities [NCET-08-0393]
- National High Technology Research and Development Program 863 [2012AA02A508]
- Specialized Research Fund for the Doctoral Program of Higher Education [20111202110004]
The combined treatment of chemotherapeutant and microRNA (miR) has been proven to be a viable strategy for enhancing chemosensitivity due to its synergistic effect for tumor therapy. However, the co-delivery of drugs and genes remains a major challenge as they lack efficient co-delivery carriers. In this study, three amphiphilic star-branched copolymers comprising polylactic acid (PLA) and polydimethylaminoethyl methacrylate (PDMAEMA) with AB(3), (AB(3))(2),and (AB(3))(3) molecular architectures were synthesized respectively by a combination of ring-opening polymerization, atom transfer radical polymerization, and click chemistry via an arm-first approach. The star copolymers possessed a low critical micelle concentration (CMC) and formed nano-sized micelles with positive surface charges in water as well as exhibiting a much lower cytotoxicity than PEI 25 kDa. Nevertheless, their gene transfection efficiency and tumor inhibition ability showed a remarkable dependence on their molecular architecture. The (AB(3))(3) architecture micelle copolymer exhibited the highest transfection efficiency, about 2.5 times higher than PEI. In addition, after co-delivering DOX and miR-21 inhibitor (miR-21i) into LN229 glioma cells, the micelles could mediate escaping miR-21i from lysosome degradation and the release of DOX to the nucleus, which significantly decreased the miR-21 expression. Moreover, co-delivery of DOX and miR-21i surprisingly exhibited an anti-proliferative efficiency compared with DOX or the miR-21i treatment alone. These results demonstrated that amphiphilic star-branched copolymers are highly promising for their combinatorial delivery of genes and hydrophobic therapeutants. (c) 2013 Elsevier Ltd. All rights reserved.
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