陈华兵教授课题组在ACS Nano(IF 12.881)再次发表通讯作者论文

陈华兵教授课题组在ACS Nano(IF=12.881)再次发表通讯作者论文(ACS Nano, 2015, DOI: 10.1021/acsnano.5b05097)。该论文是在近期已有的肿瘤光热治疗基础上(Adv Mater, 2015, 27, 3874-3882;ACS Nano, 2015, 9, 7874-7885;Adv. Funct. Mater. 2015, 25, 59-67等),进一步在逆转肿瘤耐药性方面取得的新进展。该工作采用聚氨基酸胶束作为药物(顺铂前药/Cypate)载体,增强耐药性细胞株对顺铂前药的摄取能力;进一步还发现光热效应有效抑制了耐药相关蛋白MRP1的表达,从而协同逆转细胞的耐药性,增强顺铂的抗肿瘤作用,进而实现耐药性肿瘤的热化疗协同消融作用。论文具体工作是由我院硕士生李艳丽等完成。

Multi-Pronged Design of Light-Triggered Nanoparticles to Overcome Cisplatin Resistance for Efficient Ablation of Resistant Tumor

Yanli Li,†, Yibin Deng,†, Xin Tian,‡, Hengte Ke,†,* Miao Guo,† Aijun Zhu,† Tao Yang,† Zhengqing Guo,‡ Zhishen Ge,§ Xiangliang Yang,‖ Huabing Chen†,‡,*
ACS Nano 2015, In press, DOI: 10.1021/acsnano.5b05097
Abstract: 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 multi-pronged 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 multi-pronged effects of light-triggered micelles cause synergistic cyototxicity against both A549 cells and A549R cells, and thus efficient ablation of cisplatin-resistant tumor without re-growth. The multi-pronged features of light-triggered micelles represent a versatile synergistic approach for the ablation of resistant tumor in the field of cancer therapy.

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