A tumor-penetrable drug nanococktail made from human histones for interventional nucleus-targeted chemophotothermal therapy of drug-resistant tumors

一种由人类组蛋白制成的可穿透肿瘤的药物纳米鸡尾酒,用于耐药肿瘤的介入性核靶向化学光热治疗

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作者:Jianquan Guo, Dongsheng Tan, Chenmei Lou, Shiying Guo, Xing Jin, Haijing Qu, Lijia Jing, Sijin Li

Abstract

Nanoparticle-based chemophotothermal therapy (CPT) is a promising treatment for multidrug resistant tumors. In this study, a drug nanococktail of DIR825@histone was developed by employing doxorubicin (DOX), NIR dye IR825 and human histones for interventional nucleus-targeted CPT of multidrug resistant tumors with an interventional laser. After localized intervention, DIR825@histone penetrated tumor tissues by transcytosis, efficiently entered tumor cells and targeted the cell nuclei. DIR825@histone also exhibited good photothermal performance and thermal-triggered drug release. Efficient multidrug resistant tumor inhibition was achieved by enhanced CPT sensitization and MDR reversion via nuclear targeting. Moreover, an interventional laser assisted DIR825@histone in inhibiting multidrug resistant tumors by promoting the sufficient delivery of laser energy inside the tumor while reducing skin injury. Therefore, DIR825@histone together with this interventional nucleus-targeted CPT strategy holds great promise for treating multidrug resistant tumors.

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