癌症免疫疗法
免疫疗法
自噬
效应器
化学
癌细胞
免疫系统
癌症研究
细胞生物学
生物
癌症
生物化学
免疫学
细胞凋亡
遗传学
作者
Yazhen Wang,Lianyi Yang,C. Yan,Yufan Du,Tinghua Li,Wenqing Yang,Lei Lei,Bin He,Huile Gao,Nicholas A. Peppas,Jun Cao
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2024-06-21
卷期号:10 (25)
标识
DOI:10.1126/sciadv.adn8079
摘要
Autophagy-targeting chimera (AUTAC) has emerged as a powerful modality that can selectively degrade tumor-related pathogenic proteins, but its low bioavailability and nonspecific distribution significantly restrict their therapeutic efficacy. Inspired by the guanine structure of AUTAC molecules, we here report supramolecular artificial Nano-AUTACs (GM NPs) engineered by AUTAC molecule GN [an indoleamine 2,3-dioxygenase (IDO) degrader] and nucleoside analog methotrexate (MTX) through supramolecular interactions for tumor-specific protein degradation. Their nanostructures allow for precise localization and delivery into cancer cells, where the intracellular acidic environment can disrupt the supramolecular interactions to release MTX for eradicating tumor cells, modulating tumor-associated macrophages, activating dendritic cells, and inducing autophagy. Specifically, the induced autophagy facilitates the released GN for degrading immunosuppressive IDO to further enhance effector T cell activity and inhibit tumor growth and metastasis. This study offers a unique strategy for building a nanoplatform to advance the field of AUTAC in tumor immunotherapy.
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