School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China.
Biomaterials. 2013 Jan;34(1):262-74. doi: 10.1016/j.biomaterials.2012.09.037. Epub 2012 Oct 6.
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.
单壁碳纳米管（SWNTs）是一种特殊的纳米材料，具有有趣的物理和化学性质，为生物医学研究和应用带来了新的机会。在这项研究中，我们成功地采用了一种新颖的策略，通过纯化、氧化、氨化和聚合，将聚乙烯亚胺（PEI）化学功能化到 SWNTs 上，然后通过 DSPE-PEG2000-Maleimide 将其与肿瘤靶向 NGR（Cys-Asn-Gly-Arg-Cys-）肽结合，通过半胱氨酸的马来酰亚胺基团和巯基，最后装载 hTERT siRNA，得到一种新型的肿瘤靶向 siRNA 递药系统，命名为 SWNT-PEI/siRNA/NGR。结果表明，SWNT-PEI/siRNA/NGR 能够有效地穿过细胞膜，在体外诱导 PC-3 细胞发生更严重的凋亡和更强的增殖抑制。此外，在荷瘤小鼠模型中，由于在肿瘤中积累更多，而在主要器官中没有明显毒性，该递药系统表现出更高的抗肿瘤活性。RNAi 和近红外（NIR）光热治疗的结合显著增强了治疗效果。总之，SWNT-PEI/siRNA/NGR 通过结合基因治疗和光热治疗，是一种新型的、有前途的抗癌系统。
