title: Star-Shaped Amphiphilic Hyperbranched Polyglycerol Conjugated with Dendritic Poly(l-lysine) for the Codelivery of Docetaxel and MMP-9 siRNA in Cancer Therapy.
abstract: The drug/gene codelivery is a promising strategy for cancer treatment. Herein, to realize the codelivery of docetaxel and MMP-9 siRNA plasmid efficiently into tumor cells, a star-shaped amphiphilic copolymer consisting of hyperbranched polyglycerol derivative (HPG-C18) and dendritic poly(l-lysine) (PLLD) was synthesized by the click reaction between azido-modified HPG-C18 and propargyl focal point PLLD. The obtained HPG-C18-PLLD could form the nanocomplexes with docetaxel and MMP-9, and the complexes showed good gene delivery ability in vitro by inducing an obvious decrease in MMP-9 protein expression in MCF-7 cells. The apoptosis assay showed that the complex could induce a more significant apoptosis to breast cancer cells than that of docetaxel or MMP-9 used alone. In vivo assay indicated that the codelivery strategy displayed a better effect on tumor inhibition. Moreover, HPG-C18-PLLD displayed lower toxicity as well as better blood compatibility compared to polyethylenimine PEI-25k, which may be the result of that HPG-C18-PLLD showed the comparative MMP-9 delivery ability in vivo compared with PEI-25k even if it showed the slight lower transfection efficiency in vitro. Therefore, HPG-C18-PLLD is a safe and effective carrier for the codelivery of drug/gene, which should be encouraged in tumor therapy.
authors.affiliation: Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University , Guangzhou 510632, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University , Guangzhou 510632, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences , Beijing 100850, China.
authors.forename: Changyong
authors.initials: C
authors.lastname: Wang
authors.affiliation: The School of Pathology and Laboratory Medicine, University of Western Australia , Perth, Australia.
authors.forename: Jiake
authors.initials: J
authors.lastname: Xu
authors.affiliation: 3D Imaging and Bioengineering Laboratory, Department of Mechanical Engineering, Curtin University , Perth, Australia.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Wu
authors.affiliation: 3D Imaging and Bioengineering Laboratory, Department of Mechanical Engineering, Curtin University , Perth, Australia.
authors.forename: Thomas Brett
authors.initials: TB
authors.lastname: Kirk
authors.affiliation: Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University , Guangzhou 510632, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Ma
authors.affiliation: Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University , Guangzhou 510632, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xue
mesh_terms: D045744:Cell Line, Tumor; D000077143:Docetaxel; D016503:Drug Delivery Systems / Q000379:methods*; D005990:Glycerol / Q000737:chemistry*; D006801:Humans; D061986:MCF-7 Cells; D009369:Neoplasms / Q000188:drug therapy / Q000628:therapy*; D011107:Polylysine / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D043823:Taxoids / Q000008:administration & dosage*
chemical_list: D011108:Polymers; D034741:RNA, Small Interfering; D043823:Taxoids; D000077143:Docetaxel; D011107:Polylysine; C043941:polyglycerol; D005990:Glycerol
keywords: co-delivery; hyperbranched polyglycerol; poly(l-lysine) dendrimer; star-shaped copolymer; tumor therapy