化学免疫疗法
免疫原性细胞死亡
阿霉素
癌症研究
免疫系统
药物输送
免疫检查点
癌症免疫疗法
材料科学
医学
癌细胞
癌症
药理学
免疫疗法
化疗
免疫学
纳米技术
内科学
作者
Mingxia Jiang,Wenqiang Chen,Wei Yu,Zhiwei Xu,Xinyue Liu,Qingmiao Jia,Xiuwen Guan,Weifen Zhang
标识
DOI:10.1021/acsami.1c10643
摘要
Chemoimmunotherapy has anchored a new blueprint for cancer management. As a burgeoning approach, immunotherapy has shifted the paradigm of traditional chemotherapy and opened up new prospects for cancer treatment. Here, a sequentially pH-responsive doxorubicin (DOX) delivery nanosystem is designed for simultaneous chemotherapy and tumor immunogenic cell death (ICD). DOX is modified into pH-sensitive cis-aconityl-doxorubicin (CAD) for being easily adsorbed by polycationic polyethylenimine (PEI), and the PEI/CAD complexes are in situ-shielded by aldehyde-modified polyethylene glycol (PEG). The PEG/PEI/CAD nanoparticles (NPs) can keep stable in neutral physiological pH during systemic circulation but will detach PEG shielding once in slightly acidic tumor extracellular pH. The exposed positive PEI/CAD complexes are endocytosed effortlessly, and CAD is then converted back to DOX by endosomal-acidity-triggered cis-aconityl cleavage. The released DOX further elicits ICD, and the moribund tumor cells will release antigens and damage-associated molecular patterns to recruit dendritic cells and activate antitumor immunity. An excellent therapeutic effect is achieved when the immune checkpoint PD-1 antibody (aPD-1) is utilized to cooperate with the PEG/PEI/CAD NPs for blocking tumor immune escape and maintaining antitumor activity of the ICD-instigated T cells. The sequentially pH-responsive DOX delivery nanosystem cooperating with immune checkpoint blockade will provide a potential strategy for cancer chemoimmunotherapy.
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