Polymer-lipid hybrid nanoparticles conjugated with anti-EGF receptor antibody for targeted drug delivery to hepatocellular carcinoma
Polymer-lipid hybrid nanoparticles conjugated with anti-EGF receptor antibody for targeted drug delivery to hepatocellular carcinoma
复制标题
聚合物-脂质杂化纳米颗粒与抗 EGF 受体抗体缀合，用于肝细胞癌靶向药物输送。
DOI：
10.2217/nnm.13.20
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发表时间：
2014-02-01
期刊：
影响因子：
5.5
通讯作者：
Guo, Yajun
中科院分区：
文献类型：
--
作者：
Gao, Jie;Xia, Yu;Guo, Yajun
目的：本研究的目的是获得阿霉素聚合物-脂质杂化纳米粒结合抗表皮生长因子受体抗体（PLNP-Mal-EGFR）用于肝细胞癌（HCC）化疗。材料与方法：采用动态光散射和荧光光谱对纳米粒进行表征。评价了纳米粒的体内外分布和抗肿瘤活性。结果与结论：与非靶向纳米颗粒（聚合物-脂质混合纳米颗粒[含有DSPE-PEG-Mal]和聚合物-脂质混合纳米颗粒[含有DSPE-mPEG]与抗EGFR Fab组合）相比，PLNP-Mal-EGFR显示出显著增强的对过表达EGFR的HCC细胞的细胞毒性。PLNP-Mal-EGFR和非靶向纳米颗粒可显著降低HCC细胞中侧群细胞的比例。PLNP-Mal-EGFR纳米粒在高表达EGFR的SMMC-7721肝癌细胞中的体内蓄积明显高于非靶向纳米粒。值得注意的是，与非靶向纳米颗粒和游离阿霉素相比，PLNP-Mal-EGFR在体内显示出显著增强的抗HCC的抗肿瘤活性。因此，PLNP-Mal-EGFR可作为HCC化疗的有效治疗方法。原件提交日期：2012年4月11日;修订版提交日期：2013年12月13日;在线发布日期：2013年5月31日
Aims: The aim of this study was to obtain adriamycin-loaded polymer-lipid hybrid nanoparticles conjugated with anti-EGF receptor antibody (PLNP-Mal-EGFR) for hepatocellular carcinoma (HCC) chemotherapy. Materials & methods: The nanoparticles were characterized by dynamic light scattering and fluorescence spectroscopy. The in vitro and in vivo distribution and anti-tumor activity of the nanoparticles were evaluated. Results & conclusion: PLNP-Mal-EGFR showed significantly enhanced cellular cytotoxicity against HCC cells overexpressing EGFR compared with nontargeted nanoparticles (polymer-lipid hybrid nanoparticles [containing DSPE-PEG-Mal] and polymer-lipid hybrid nanoparticles [containing DSPE-mPEG] combined with anti-EGFR Fab). PLNP-Mal-EGFR and nontargeted nanoparticles could significantly reduce the proportion of side-population cells in HCC cells. The in vivo accumulation of PLNP-Mal-EGFR was obviously higher than that of nontargeted nanoparticles in SMMC-7721 HCC cells overexpressing EGFR. Notably, PLNP-Mal-EGFR showed significantly enhanced anti-tumor activity against HCC in vivo compared with nontargeted nanoparticles and free adriamycin. Therefore, PLNP-Mal-EGFR may serve as an effective therapeutic approach for HCC chemotherapy. Original submitted 11 April 2012; Revised submitted 13 December 2013; Published online 31 May 2013