A micellar cisplatin prodrug simultaneously eliminates both cancer cells and cancer stem cells in lung cancer
A micellar cisplatin prodrug simultaneously eliminates both cancer cells and cancer stem cells in lung cancer
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胶束顺铂前药同时消除肺癌中的癌细胞和癌症干细胞
DOI：
10.1039/c7bm00278e
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发表时间：
2017
影响因子：
6.6
通讯作者：
Jun Wang
中科院分区：
文献类型：
--
作者：
Yan-Hua Zhu;Chun-Yang Sun;Song Shen;Malik I. U. Khan;Yang-Yang Zhao;Yang Liu;Yu-Cai Wang;Jun Wang
铂类化疗作为肺癌的一线治疗，在临床上存在选择性不足、毒副作用严重和耐药等问题。在这项研究中，我们开发了一个两亲性的前药顺铂-聚（乙二醇）-嵌段-聚己内酯，并证明了前药形成胶束纳米粒子，NPPt（IV），平均直径为100 nm。NPPt（IV）释放铂在响应细胞内的酸性和还原性环境，并反过来诱导显着的抗增殖活性在肺癌细胞。更重要的是，NPPt（IV）对CD 133+肺癌干细胞（CSC）表现出显着的抑制作用，并抑制体内肿瘤生长。与最终富集CSC的顺铂治疗不同，NPPt（IV）治疗可防止CD 133+肺CSC在肿瘤中的积累。因此，靶向CSC和非CSC的NPPt（IV）模拟物可能代表改善主要针对肿瘤块群体的常规抗癌疗法的上级策略。
Platinum-based chemotherapy as first-line treatment for lung cancers encounters insufficient selectivity, severe side effects and drug resistance in clinics. In this study, we developed an amphiphilic prodrug of cisplatin-poly(ethylene glycol)-block-polycaprolactone and demonstrated that the prodrug formed micellar nanoparticles, NPPt(IV), with an average diameter of ∼100 nm. NPPt(IV) released platinum in response to the intracellular acidic and reductive environment, and in turn induced significant anti-proliferative activity in lung cancer cells. More importantly, NPPt(IV) exhibited a prominent inhibitory effect on CD133+ lung cancer stem cells (CSCs) and suppressed tumor growth in vivo. Unlike cisplatin treatment which eventually enriches CSCs, NPPt(IV) treatment prevents the accumulation of CD133+ lung CSCs in tumors. Therefore, NPPt(IV) simutaneously targeting CSCs and non-CSCs might represent a superior strategy to improve conventional anticancer therapy directed predominantly to tumor bulk populations.