Leng Dewen, Hu Jun, Huang Xiaolong, He Wei, Wang Yuan, Liu Mei
Department of Critical Care Medicine, Wuhan No. 1 Hospital, 215 Zhongshan Street, Wuhan 430022, China.
Department of Physical Examination, Wuhan Hospital for Occupational Disease Prevention and Treatment, 18-20 Jianghanbei Road, Wuhan 430016, China.
J Nanosci Nanotechnol. 2018 Aug 1;18(8):5242-5251. doi: 10.1166/jnn.2018.15424.
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.
肺癌是全球最致命的癌症，其发生和复发归因于肺癌干细胞（CSCs）。有证据表明，癌细胞能够自发地转变为CSCs，因此同时清除肺CSCs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CSCs和癌细胞中均过度表达。本研究开发了与EGFR适体偶联的沙利霉素聚乙二醇2000-二硬脂酰磷脂酰乙醇胺纳米胶束（M-SAL-EGFR），以杀死肺CSCs和癌细胞。通过基于脂质膜的方法制备了尺寸为24 nm的M-SAL-EGFR。EGFR在肺CSCs和癌细胞中过度表达。结果显示，M-SAL-EGFR能够有效地结合EGFR过表达的肺CSCs和癌细胞，并比非靶向的M-SAL和沙利霉素诱导更强的细胞毒性作用。与M-SAL和沙利霉素相比，给肺癌异种移植小鼠施用M-SAL-EGFR能更有效地抑制肿瘤生长。因此，EGFR适体能够促进沙利霉素有效地递送至肺癌。我们的结果还表明，M-SAL-EGFR是一种同时靶向肺CSCs和癌细胞的有前景的方法。
