肿瘤微环境
免疫原性细胞死亡
癌症研究
阿霉素
化学
药物输送
免疫疗法
化疗
免疫系统
医学
免疫学
内科学
肿瘤细胞
有机化学
作者
Yuelin Fang,Susu Huang,Qiaoying Hu,Jicheng Zhang,Julia A. King,Yanqing Wang,Zhijian Wei,Jinghui Lu,Zhijing He,Xinru Kong,Xiaoye Yang,Jianbo Ji,Junjie Li,Guangxi Zhai,Lei Ye
出处
期刊:ACS Nano
[American Chemical Society]
日期:2023-10-26
卷期号:17 (24): 24883-24900
被引量:11
标识
DOI:10.1021/acsnano.3c05898
摘要
Surgical resection is the first-line therapy for breast cancer. However, residual tumor cells and the highly immunosuppressive tumor microenvironment (TME) continue to have a serious impact on tumor recurrence and metastasis postresection. Implantation of an in situ hydrogel system postresection has shown to be an effective treatment with great clinical potential. Herein, an injectable zwitterionic hydrogel system was developed for local drug delivery with enhanced immune activation and prevention of tumor recurrence. Driven by electrostatic interactions, poly(sulfobetaine methacrylate) (PSBMA) self-assembles into a hydrogel in saline, achieving low protein adsorption and tunable biodegradability. The chemotherapy drug doxorubicin (DOX) was loaded into copper peroxide nanoparticles (CuO2/DOX), which were coated with macrophage membranes to form tumor-targeting nanoparticles (M/CuO2/DOX). Next, M/CuO2/DOX and the stimulator of interferon genes (STING) agonist 2′,3′-cGAMP were coloaded into PSBMA hydrogel (Gel@M/CuO2/DOX/STING). The hydrophilic STING agonist was first released by diffusion from hydrogel to activate the STING pathway and upregulate interferon (IFN) signaling related genes, remodeling the immunosuppressive TME. Then, M/CuO2/DOX targeted the residual tumor cells, combining with DOX-induced DNA damage, immunogenic tumor cell death, and copper death. Hence, this work combines chemodynamic therapy with STING pathway activation in TME, encouraging residual tumor cell death, promoting the maturation of dendritic cells, enhancing tumor-specific CD8+ T cell infiltration, and preventing postoperative recurrence and metastasis.
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