Synergistic anticancer effect of RNAi and photothermal therapy mediated by functionalized single-walled carbon nanotubes

作者:Wang, Lei; Shi, Jinjin; Zhang, Hongling; Li, Haixia; Gao, Yan; Wang, Zhenzhen; Wang, Honghong; Li, Lulu; Zhang, Chaofeng; Chen, Chengqun; Zhang, Zhenzhong*; Zhang, Yun
来源:Biomaterials, 2013, 34(1): 262-274.
DOI:10.1016/j.biomaterials.2012.09.037

摘要

Single-walled carbon nanotubes (SWNTs) are special nano-materials which exhibit interesting physical and chemical properties, presenting new opportunities for biomedical research and applications. In this study, we have successfully adopted a novel strategy to chemically functionalize SWNTs with polyethylenimine (PEI) through purification, oxidation, amination and polymerization, which were then bound by DSPE-PEG2000-Maleimide for further conjugation with the tumor targeting NGR (Cys-Asn-Gly-Arg-Cys-) peptide via the maleimide group and sulfhydryl group of cysteine, and finally hTERT siRNA was loaded to obtain a novel tumor targeting siRNA delivery system, designated as SWNT-PEI/siRNA/NGR. The results showed that SWNT-PEI/siRNA/NGR could efficiently cross cell membrane, induced more severe apoptosis and stronger suppression in proliferation of PC-3 cells in vitro. Furthermore, in tumor-bearing mice model the delivery system exhibited higher antitumor activity due to more accumulation in tumor without obvious toxicity in main organs. The combination of RNAi and near-infrared (NIR) photothermal therapy significantly enhanced the therapeutic efficacy. In conclusion, SWNT-PEI/siRNA/NGR is a novel and promising anticancer system by combining gene therapy and photothermal therapy.