肿瘤微环境
免疫原性细胞死亡
化学
癌症研究
顺铂
光动力疗法
肿瘤缺氧
药物输送
药品
联合疗法
免疫疗法
药理学
免疫系统
化疗
医学
免疫学
放射治疗
有机化学
外科
内科学
肿瘤细胞
作者
Guanghui Hou,Wei Wang,Min Guo,Jinlei Wang,Yaping Wang,Aili Suo,Junmin Qian
标识
DOI:10.1016/j.cej.2022.135993
摘要
Precise manipulation of reactive oxygen species (ROS) breakthrough threshold exhibits great potential in destroying solid tumors, reprogramming "immune-cold" tumor and potentiating immunotherapy. However, it is still challenging to develop efficient ROS initiation devices. Herein, we propose a pioneering "grafting from" drug coordination polymerization strategy and develop a fully-coordinated and full-active Cu2O/drug core/shell nanoparticles for multimodal cancer therapy. Chemotherapeutic drug cisplatin (CDDP) and photosensitizer indocyanine green (ICG) were loaded onto the surface of hydrazided hyaluronic acid-decorated Cu2O (HA-Cu2O) nanoparticles through an infinite hydrazide-cisplatin-sulfonic acid coordination mechanism, obtaining CDDP/ICG-coloaded HA-Cu2O (HCCI) nanoplatform. The HCCI nanoplatform exhibited a rapid acid-responsive dissociation behavior and released ICG, Cu+ and CDDP to achieve efficient triple combined photodynamic therapy/chemodynamic therapy/chemotherapy. Importantly, such a combination induced efficient immunogenic cell death cascade mediated by powerful ROS storm to reprogram "immune-cold" tumors and potentiate immunotherapy. The combination of HCCI nanoplatform and αPD-1 not only eradicated primary tumors but effectively inhibited distal tumor growth, lung metastasis and tumor recurrence through reprogramming tumor microenvironment and activating CD8+ T cell antitumor immunity. Collectively, we have presented a drug coordination polymerization loading strategy to develop a robust multimodal antitumor nanoplatform, and this study provides a new direction for the design of nanodrug delivery systems.
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