肿瘤微环境
免疫系统
癌症研究
免疫疗法
免疫原性细胞死亡
癌细胞
癌症免疫疗法
光热治疗
材料科学
癌症
CD8型
肿瘤坏死因子α
生物
医学
免疫学
纳米技术
内科学
作者
Liqun Yang,Yan Wang,Weijian Liu,He Ma,Bo Yang,Kun Shao,Saran Long,Wen Sun,Jianjun Du,Jiangli Fan,Bin Liu,Lei Wang,Xiaojun Peng
出处
期刊:Biomaterials
[Elsevier]
日期:2023-05-01
卷期号:296: 122089-122089
被引量:16
标识
DOI:10.1016/j.biomaterials.2023.122089
摘要
Cancer immunotherapy, despite its enormous application prospect, is trapped in the abnormal lactic acid metabolism of tumor cells that usually causes an immunosuppressive tumor microenvironment (ITM). Inducing immunogenic cell death (ICD) not only sensitizes cancer cells to carcer immunity, but also leads to a great increase in tumor-specific antigens. It improves tumor condition from "immune-cold" to "immune-hot". Herein, a near-infrared photothermal agent NR840 was developed and encapsulated into tumor-targeted polymer DSPE-PEG-cRGD and carried lactate oxidase (LOX) by electrostatic interaction, forming self-assembling "nano-dot" PLNR840 with high loading capacity for synergistic antitumor photo-immunotherapy. In this strategy, PLNR840 was swallowed by cancer cells, then dye NR840 was excited at 808 nm to generate heat inducing tumor cell necrosis, which further caused ICD. LOX could serve as a catalyst, reducing lactic acid efflux via regulation of cell metabolism. More importantly, the consumption of intratumoral lactic acid could substantially reverse ITM, including promoting the polarization of tumor-associated macrophages from M2 to M1 type, inhibiting the viability of regulatory T cells for sensitizing photothermal therapy (PTT). After the combination of αPD-L1 (programmed cell death protein ligand 1), PLNR840 restored CD8+ T-cell activity that thoroughly cleaned the pulmonary metastasis of breast cancer in 4T1 mouse model and cured hepatocellular carcinoma in Hepa1-6 mouse model. This study provided an effective PTT strategy to boost "immune-hot" and reprogrammed tumor metabolism for antitumor immunotherapy.
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