Multipronged Design of Light-Triggered Nanoparticles To Overcome Cisplatin Resistance for Efficient Ablation of Resistant Tumor
Multipronged Design of Light-Triggered Nanoparticles To Overcome Cisplatin Resistance for Efficient Ablation of Resistant Tumor
复制标题
光触发纳米颗粒的多管齐下设计，克服顺铂耐药性，有效消融耐药肿瘤
DOI：
10.1021/acsnano.5b05097
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发表时间：
2015-10-01
期刊：
影响因子：
17.1
通讯作者：
Chen, Huabing
中科院分区：
文献类型：
--
作者：
Li, Yanli;Deng, Yibin;Chen, Huabing
化疗药物在肿瘤治疗中经常遇到多重耐药。已经探索了通过静脉内给药消融耐药肿瘤的策略，但成功有限。在这项工作中，合理设计的光触发的纳米粒子具有多管齐下的物理化学和生物学特性，通过组装铂（IV）前药和菁染料（Cypate）的共聚物内的顺铂耐药性的有效消融顺铂耐药肿瘤。胶束表现出良好的光稳定性，持续释放，优选的肿瘤蓄积，并增强细胞摄取，减少流出A549细胞和耐药A549R细胞。此外，近红外光不仅引发胶束的光热效应，产生显著的光热细胞毒性，而且还导致胶束和可还原活化的Pt（IV）前药通过溶酶体破坏而进入细胞质的胞内易位，以及对药物外排转运蛋白的表达的显著抑制，多药耐药相关蛋白1（MRP1）用于进一步逆转A549 R细胞的耐药性。因此，光触发胶束的多管齐下的作用引起对A549细胞和A549R细胞的协同细胞毒性，从而有效消融顺铂耐药肿瘤而不再生。光引发胶束的多管齐下的特性代表了在癌症治疗领域中用于消融耐药肿瘤的通用协同方法。
Chemotherapeutic drugs frequently encounter multiple drug resistance in the field of cancer therapy. The strategy has been explored with limited success for the ablation of drug-resistant tumor via intravenous administration. In this work, the rationally designed light-triggered nanoparticles with multipronged physicochemical and biological features are developed to overcome cisplatin resistance via the assembly of Pt(IV) prodrug and cyanine dye (Cypate) within the copolymer for efficient ablation of cisplatin-resistant tumor. The micelles exhibit good photostability, sustained release, preferable tumor accumulation, and enhanced cellular uptake with reduced efflux on both A549 cells and resistant A549R cells. Moreover, near-infrared light not only triggers the photothermal effect of the micelles for remarkable photothermal cytotoxicity, but also leads to the intracellular translocation of the micelles and reduction-activable Pt(IV) prodrug into cytoplasm through the lysosomal disruption, as well as the remarkable inhibition on the expression of a drug-efflux transporter, multidrug resistance-associated protein 1 (MRP1) for further reversal of drug resistance of A549R cells. Consequently, the multipronged effects of light-triggered micelles cause synergistic cytotoxicity against both A549 cells and A549R cells, and thus efficient ablation of cisplatin-resistant tumor without regrowth. The multipronged features of light-triggered micelles represent a versatile synergistic approach for the ablation of resistant tumor in the field of cancer therapy.