Targeted Enrichment of Enzyme-Instructed Assemblies in Cancer Cell Lysosomes Turns Immunologically Cold Tumors Hot
Dr. Shenglu Ji
Frontiers Science Center for Cell Responses, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, and College of Life Sciences, Nankai University, Tianjin, 300071 China
The Key Laboratory of Biomedical Materials, School of Life Science and Technology, Xinxiang Medical University, Xinxiang, 453003 China
Search for more papers by this authorDr. Jun Li
Frontiers Science Center for Cell Responses, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, and College of Life Sciences, Nankai University, Tianjin, 300071 China
Search for more papers by this authorXingchen Duan
Frontiers Science Center for Cell Responses, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, and College of Life Sciences, Nankai University, Tianjin, 300071 China
Search for more papers by this authorJingtian Zhang
Frontiers Science Center for Cell Responses, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, and College of Life Sciences, Nankai University, Tianjin, 300071 China
Search for more papers by this authorYufan Zhang
Frontiers Science Center for Cell Responses, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, and College of Life Sciences, Nankai University, Tianjin, 300071 China
Search for more papers by this authorMengqing Song
The Key Laboratory of Biomedical Materials, School of Life Science and Technology, Xinxiang Medical University, Xinxiang, 453003 China
Search for more papers by this authorDr. Songge Li
The Key Laboratory of Biomedical Materials, School of Life Science and Technology, Xinxiang Medical University, Xinxiang, 453003 China
Search for more papers by this authorProf. Hongli Chen
The Key Laboratory of Biomedical Materials, School of Life Science and Technology, Xinxiang Medical University, Xinxiang, 453003 China
Search for more papers by this authorCorresponding Author
Prof. Dan Ding
Frontiers Science Center for Cell Responses, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, and College of Life Sciences, Nankai University, Tianjin, 300071 China
Search for more papers by this authorDr. Shenglu Ji
Frontiers Science Center for Cell Responses, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, and College of Life Sciences, Nankai University, Tianjin, 300071 China
The Key Laboratory of Biomedical Materials, School of Life Science and Technology, Xinxiang Medical University, Xinxiang, 453003 China
Search for more papers by this authorDr. Jun Li
Frontiers Science Center for Cell Responses, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, and College of Life Sciences, Nankai University, Tianjin, 300071 China
Search for more papers by this authorXingchen Duan
Frontiers Science Center for Cell Responses, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, and College of Life Sciences, Nankai University, Tianjin, 300071 China
Search for more papers by this authorJingtian Zhang
Frontiers Science Center for Cell Responses, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, and College of Life Sciences, Nankai University, Tianjin, 300071 China
Search for more papers by this authorYufan Zhang
Frontiers Science Center for Cell Responses, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, and College of Life Sciences, Nankai University, Tianjin, 300071 China
Search for more papers by this authorMengqing Song
The Key Laboratory of Biomedical Materials, School of Life Science and Technology, Xinxiang Medical University, Xinxiang, 453003 China
Search for more papers by this authorDr. Songge Li
The Key Laboratory of Biomedical Materials, School of Life Science and Technology, Xinxiang Medical University, Xinxiang, 453003 China
Search for more papers by this authorProf. Hongli Chen
The Key Laboratory of Biomedical Materials, School of Life Science and Technology, Xinxiang Medical University, Xinxiang, 453003 China
Search for more papers by this authorCorresponding Author
Prof. Dan Ding
Frontiers Science Center for Cell Responses, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, and College of Life Sciences, Nankai University, Tianjin, 300071 China
Search for more papers by this authorGraphical Abstract
We report an alkaline phosphatase (ALP)-responsive lysosomal membrane permeabilization (LMP) inducer, which can specifically accumulate in cancer cell lysosomes for evoking immunogenic cell death (ICD) and converting immunologically cold tumors into hot tumors.
Abstract
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.
Conflict of interest
The authors declare no conflict of interest.
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