数字农科院2.0

Tumor-Penetrating and Mitochondria-Targeted Drug Delivery Overcomes Doxorubicin Resistance in Lung Cancer

文献类型： 外文期刊

作者： Zhou, Meng-Xue;Zhang, Jia-Yu;Cai, Xiao-Meng;Dou, Rui;Ruan, Li-Fo;Yang, Wen-Jiang;Lin, Wen-Chu;Chen, Jun;Hu, Yi

作者机构：

关键词： Doxorubicin;NIR;pH-dual sensitive nanoparticles;Tumor penetration;Mitochondria;Drug resistance

期刊名称： CHINESE JOURNAL OF POLYMER SCIENCE

ISSN： 0256-7679

年卷期： 2022 年

页码：

收录情况： SCIE（2022版） ; EI（2022版） ; CSCD（2021-2022年度） ; 科技核心（2021版）

摘要： As one of the major challenges in tumor chemotherapy, multidrug resistance typically correlates with the poor drug penetration within tumor tissues and drug efflux by the ATP-driven efflux pumps in tumor cells. Herein, we design a kind of near-infrared (NIR) light- and acidity-activated micellar iPUTDN nanoparticle for mitochondria-targeting doxorubicin (DOX) delivery to combat DOX resistance in small-cell lung cancer. While the PEGylated iPUTDN nanoparticles can keep stealth in blood circulation, NIR irradiation at the tumor region can peel off the PEG shell from the nanoparticles, and the exposed iRGD can facilitate deep tumor penetration of the nanoparticles. After being internalized by DOX-resistant H69AR cells, the poly(beta-aminoester)s (PAE)-based nanoparticles can release the triphenylphosphonium (TPP)-conjugated DOX (TDOX) into the cytosol, which can further accumulate in mitochondria with the aid of TPP. Consequently, the mitochondrial membrane potential and ATP content are both reduced in DOX-resistant H69AR cells. The in vivo therapeutic results show that TDOX-loaded nanoparticles with the aid of NIR light irradiation can effectively suppress the DOX-resistant small-cell lung cancer without noticeable adverse effects.

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