Star-shaped cyclodextrin-poly(l-lysine) derivative co-delivering docetaxel and MMP-9 siRNA plasmid in cancer therapy |
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Authors: | Tao Liu Wei Xue Bo Ke Min-Qiang Xie Dong Ma |
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Institution: | 1. Department of Otolaryngology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China;2. Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China;3. Jiangxi Key Laboratory of Hematological Oncology and Cell Biology, Jiangxi Provincial People''s Hospital, Nanchang 330006, China |
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Abstract: | A new cyclodextrin derivative (CD-PLLD) consisting of a β-cyclodextrin core and poly(l-lysine) dendron arms was prepared by the click conjugation of per-6-azido-b-cyclodextrin with propargyl focal point poly(l-lysine) dendron of third generation, and then used for docetaxel (DOC) and the best siRNA plasmid targeting MMP-9 (pMR3) co-delivery. Different from commonly used amphiphilic copolymers with cationic character, the as obtained cyclodextrin derivative may be used directly for the combinatorial delivery of nucleic acid and lipophilic anticancer drugs without a complicated micellization process. It was found that CD-PLLD/pMR3 nanocomplex showed a good gene transfection efficiency in vitro, and could mediate the reduce of MMP-9 protein in HNE-1 cells. For co-delivery analysis, the obtained CD-PLLD/DOC/pMR3 complexes could induce a more significant apoptosis than DOC or pMR3 used only, and decreased invasive capacity of HNE-1 cells. Moreover, the star-shaped copolymer exhibited better blood compatibility and lower cytotoxicity compared to PEI-25k in the hemolysis and MTT assays, which should be encouraged in nasopharyngeal cancer therapy. |
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Keywords: | Co-delivery Star polymers Poly(l-lysine) dendron arms Nasopharyngeal cancer |
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