NIR‐Light‐Triggered Mild‐Temperature Hyperthermia to Overcome the Cascade Cisplatin Resistance for Improved Resistant Tumor Therapy
Mingmao Chen, Yulei Fu, Y. Liu, Baihe Zhang, Xiaorong Song, Xinchun Chen, Zipeng Zhu, Hang Gao, Jianmin Yang, Xianai Shi
Abstract
Abstract Currently, cisplatin resistance has been recognized as a multistep cascade process for its clinical chemotherapy failure. Hitherto, it remains challenging to develop a feasible and promising strategy to overcome the cascade drug resistance (CDR) issue for achieving fundamentally improved chemotherapeutic efficacy. Herein, a novel self‐assembled nanoagent is proposed, which is constructed by Pt(IV) prodrug, cyanine dye (cypate), and gadolinium ion (Gd 3+ ), for systematically conquering the cisplatin resistance by employing near‐infrared (NIR) light activated mild‐temperature hyperthermia in tumor targets. The proposed nanoagents exhibit high photostability, GSH/H + ‐responsive dissociation, preferable photothermal conversion, and enhanced cellular uptake performance. In particular, upon 785‐nm NIR light irradiation, the generated mild temperature of ≈ 43 °C overtly improves the cell membrane permeability and drug uptake, accelerates the disruption of intracellular redox balance, and apparently enhances the formation of Pt‐DNA adducts, thereby effectively overcoming the CDR issue and achieves highly improved therapeutic efficacy for cisplatin‐resistant tumor ablation.