期刊
ACS APPLIED MATERIALS & INTERFACES
卷 8, 期 20, 页码 12609-12619出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.6b01611
关键词
tumor therapy; co-delivery; star-shaped copolymer; hyperbranched polyglycerol; poly(L-lysine) dendrimer
资金
- National Natural Science Foundation of China [31271019, 51573071]
- Natural Science Foundation of Guangdong Province [S2013030013315, 2014A030313361]
- Pearl River S&T Nova Program of Guangzhou [201506010069]
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.
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