Promoted Delivery of Salinomycin to Lung Cancer Through Epidermal Growth Factor Receptor Aptamers Coupled DSPE-PEG2000 Nanomicelles
Promoted Delivery of Salinomycin to Lung Cancer Through Epidermal Growth Factor Receptor Aptamers Coupled DSPE-PEG2000 Nanomicelles
复制标题
通过表皮生长因子受体适体偶联 DSPE-PEG2000 纳米胶束促进盐霉素向肺癌的递送
DOI：
10.1166/jnn.2018.15424
复制
发表时间：
2018
影响因子：
--
通讯作者：
Liu M
中科院分区：
文献类型：
--
作者：
Leng Dewen;Liu Mei;Hu Jun;Huang Xiaolong;He Wei;Wang Yuan;Leng DW;Liu M
肺癌是世界上最致命的癌症，其发生和复发归因于肺癌干细胞（CSCs）。有证据表明，癌细胞可以自发地转变为CSC，因此同时消除肺CSC和癌细胞对于实现肺癌的有效治疗至关重要。在肺癌中，表皮生长因子受体（EGFR）在CSC和癌细胞中过表达。本研究开发了盐霉素聚乙二醇2000-二硬脂酰磷脂酰乙醇胺纳米胶束与EGFR适配体（M-SAL-EGFR）结合，以杀死肺CSC和癌细胞。通过基于脂质膜的方法制备24 nm大小的M-SAL-EGFR。EGFR在肺CSC和癌细胞中过表达。结果表明，M-SAL-EGFR能有效地与EGFR过表达的肺癌细胞和肿瘤细胞结合，诱导的细胞毒作用明显强于非靶向的M-SAL和盐霉素。与M-SAL和盐霉素相比，M-SAL-EGFR在具有肺癌异种移植物的小鼠中的施用更有效地抑制肿瘤生长。因此，EGFR适体能够促进盐霉素向肺癌的有效递送。我们的研究结果还表明，M-SAL-EGFR代表了靶向肺CSC和癌细胞的有前途的方法。
Initiation and recurrence of lung cancer, the most fatal cancer worldwide, are attributed to lung cancer stem cells (CSCs). Evidence suggests that cancer cells can be turned into CSCs in a spontaneous way, and therefore simultaneous elimination of lung CSCs and cancer cells is crucial to achieve effective therapy of lung cancer. In lung cancer, epidermal growth factor receptor (EGFR) is overexpressed in both CSCs and cancer cells. The present study developed salinomycin poly(ethylene glycol) 2000-distearoylphosphatidylethanolamine nanomicelles conjugated with EGFR aptamers (M-SAL-EGFR) to kill lung CSCs and cancer cells. The 24 nm sized M-SAL-EGFR was prepared by a lipid film based method. The EGFR was overexpressed in lung CSCs and cancer cells. Results revealed that the M-SAL-EGFR could efficiently bind to EGFR-overexpressing lung CSCs and cancer cells, and induced enhanced cyotoxic effect than non-targeted M-SAL and salinomycin. Administration of M-SAL-EGFR in mice with lung cancer xenograft inhibited tumor growth more effectively compared with M-SAL and salinomycin. The EGFR aptamers were thus able to promote effective salinomycin delivery to lung cancer. Our results also suggest that the M-SAL-EGFR represents a promising approach for targeting both lung CSCs and cancer cells.