Star-shaped cyclodextrin-poly(L-lysine) derivative co-delivering docetaxel and MMP-9 siRNA plasmid in cancer therapy

A new cyclodextrin derivative (CD-PLLD) consisting of a P-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 CDPLLD/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 MU assays, which should be encouraged in nasopharyngeal cancer therapy. 2014 Elsevier Ltd. All rights reserved.