Star-branched amphiphilic PLA-b-PDMAEMA copolymers for co-delivery of miR-21 inhibitor and doxorubicin to treat glioma

详细信息    查看全文

• 作者：Xiaomin Qian ; Lixia Long ; Zhendong Shi ; Chaoyong Liu ; Mingzhe Qiu ; Jing Sheng ; Peiyu Pu ; Xubo Yuan ; Yu Ren ; Chunsheng Kang
• 关键词：Star-branched copolymer ; Polylactic acid ; Polydimethylaminoethyl methacrylate ; miR-21 ; Co-delivery ; Synergistic effects
• 刊名：Biomaterials
• 出版年：February, 2014
• 年：2014
• 卷：35
• 期：7
• 页码：2322-2335
• 全文大小：5142 K

文摘

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 AB₃, (AB₃)₂,and (AB₃)₃ molecular architectures were synthesized respectively by a combination of ring-opening polymerization, atom transfer radical polymerization, and click chemistry via an 鈥渁rm-first鈥?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聽kDa. Nevertheless, their gene transfection efficiency and tumor inhibition ability showed a remarkable dependence on their molecular architecture. The (AB₃)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.