Star-branched amphiphilic PLA-b-PDMAEMA copolymers for co-delivery of miR-21 inhibitor and doxorubicin to treat glioma
Abstract 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 car...
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Published in | Biomaterials Vol. 35; no. 7; pp. 2322 - 2335 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Netherlands
Elsevier Ltd
01.02.2014
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Subjects | |
Online Access | Get full text |
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Summary: | Abstract 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 “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 (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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0142-9612 1878-5905 |
DOI: | 10.1016/j.biomaterials.2013.11.039 |