期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 60, 期 52, 页码 26994-27004出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202110512
关键词
alkaline phosphatase; enzyme-instructed self-assembly; immunologically cold; hot tumors; lysosomal membrane permeabilization; supramolecular self-assembling peptide
资金
- National Key R&D Program of China (Intergovernmental Cooperation Project) [2017YFE0132200]
- NSFC [51961160730, 51873092, 81901874]
- Tianjin Science Fund for Distinguished Young Scholars [19JCJQJC61200]
- PhD Start-up Fund of Natural Science Foundation [505337]
This study introduces a novel LMP inducer named TPE-Py-pYK(TPP)pY, which can effectively convert immunologically cold tumors to hot by inducing ICD, providing a new strategy for cancer immunotherapy.
Lysosome-relevant cell death induced by lysosomal membrane permeabilization (LMP) has recently attracted increasing attention. However, nearly no studies show that currently available LMP inducers can evoke immunogenic cell death (ICD) or convert immunologically cold tumors to hot. Herein, we report a LMP inducer named TPE-Py-pYK(TPP)pY, which can respond to alkaline phosphatase (ALP), leading to formation of nanoassembies along with fluorescence and singlet oxygen turn-on. TPE-Py-pYK(TPP)pY tends to accumulate in ALP-overexpressed cancer cell lysosomes as well as induce LMP and rupture of lysosomal membranes to massively evoke ICD. Such LMP-induced ICD effectively converts immunologically cold tumors to hot as evidenced by abundant CD8(+) and CD4(+) T cells infiltration into the cold tumors. Exposure of ALP-catalyzed nanoassemblies in cancer cell lysosomes to light further intensifies the processes of LMP, ICD and cold-to-hot tumor conversion. This work thus builds a new bridge between lysosome-relevant cell death and cancer immunotherapy.
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