Synergistic anticancer effect of RNAi and photothermal therapy mediated by functionalized single-walled carbon nanotubes
Synergistic anticancer effect of RNAi and photothermal therapy mediated by functionalized single-walled carbon nanotubes
复制标题
功能化单壁碳纳米管介导的RNAi和光热疗法的协同抗癌作用
DOI：
10.1016/j.biomaterials.2012.09.037
复制
发表时间：
2013-01-01
期刊：
影响因子：
14
通讯作者：
Zhang, Yun
中科院分区：
文献类型：
--
作者：
Wang, Lei;Shi, Jinjin;Zhang, Yun
单壁碳纳米管（SWNTs）是一种特殊的纳米材料，具有独特的物理和化学性质，为生物医学的研究和应用提供了新的机遇。在本研究中，我们采用了一种新的策略，通过纯化、氧化、胺化和聚合，将单壁碳纳米管与聚乙烯亚胺（PEI）化学功能化，然后将其与DSPE-PEG 2000-Maleimide结合，进一步与肿瘤靶向NGR偶联（Cys-Asn-Gly-Arg-Cys-）肽通过半胱氨酸的马来酰亚胺基和巯基，最后负载hTERTsiRNA，得到一种新型的肿瘤靶向siRNA递送系统SWNT-PEI/siRNA/NGR。结果表明，SWNT-PEI/siRNA/NGR在体外能有效地穿过细胞膜，诱导PC-3细胞发生严重的凋亡，并对PC-3细胞的增殖有较强的抑制作用。在荷瘤小鼠模型中，由于在肿瘤中有较多的蓄积，该给药系统显示出较高的抗肿瘤活性，且对主要器官无明显毒性。RNA干扰和近红外（NIR）光热疗法的结合显着增强了治疗效果。结论：SWNT-PEI/siRNA/NGR是一种将基因治疗与光热治疗相结合的新型抗肿瘤系统。(C)2012爱思唯尔有限公司保留所有权利。
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. (C) 2012 Elsevier Ltd. All rights reserved.