光热治疗
免疫原性细胞死亡
阿霉素
免疫原性
肿瘤微环境
癌症研究
光热效应
材料科学
免疫系统
钙网蛋白
免疫疗法
纳米囊
背向效应
癌症
化疗
癌细胞
细胞
癌症免疫疗法
医学
细胞凋亡
纳米技术
免疫学
生物
纳米颗粒
细胞生物学
外科
内科学
内质网
作者
Yayu Wen,Xu Chen,Xufeng Zhu,Youcong Gong,Guanglong Yuan,Xiuying Qin,Jie Liu
标识
DOI:10.1021/acsami.9b17137
摘要
Inducing immunogenic cell death (ICD) that enhances the immunogenicity of dead cancer cells is a new strategy for tumor immunotherapy, but efficiently triggering ICD is the biggest obstacle to achieving this strategy, especially for distant and deep-seated tumors. Here, a new therapeutic system (Pd-Dox@TGMs NPs) that can effectively trigger ICD by combining chemotherapy and photothermal therapy was designed. The nanosystem was fabricated by integrating doxorubicin (Dox) and a photothermal reagent palladium nanoparticles (Pd NPs) into amphiphile triglycerol monostearates (TGMs), which showed specific accumulation, deep penetration, and activation in response to the tumoral enzymatic microenvironment. It was proved that codelivery of Dox and Pd NPs not only effectively killed CT26 cells through chemotherapy and photothermal therapy but also promoted the release of dangerous signaling molecules, such as high mobility group box 1, calreticulin, and adenosine triphosphate, improving the immunogenicity of dead tumor cells. The effective ICD induction mediated by Pd-Dox@TGMs NPs boosted the PD-L1 checkpoint blockade effect, which efficiently improved the infiltration of toxic T lymphocytes at the tumor site and showed excellent tumor treatment effects to both primary and abscopal tumors. Therefore, this work provides a simple and effective immunotherapeutic strategy by combining chemical-photothermal therapy to enhance immune response.
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