生物正交化学
上睑下垂
化学
肽
癌细胞
膜
生物物理学
点击化学
生物化学
组合化学
癌症
炎症体
生物
受体
遗传学
作者
Shenglu Ji,Tengwu Pan,Kaiyuan Wang,Weiqi Zai,Ruikang Jia,Sheng Wang,Shaorui Jia,Dan Ding,Yang Shi
标识
DOI:10.1002/anie.202415735
摘要
Enrichment of photosensitizers (PSs) on cancer cell membranes via bioorthogonal reactions is considered to be a very promising therapeutic modality. However, azide‐modified sugars‐based metabolic labeling processes usually lack targeting and the labeling speed is relatively slow. Moreover, it has been rarely reported that membrane‐anchoring pure type‐I PSs can induce cancer cell pyroptosis. Here, we report an alkaline phosphatase (ALP) and cholecystokinin‐2 receptor (CCK2R) dual‐targeting peptide named DBCO‐pYCCK6, which can selectively and rapidly self‐assemble on cancer cell membrane, and then bioorthogonal enrich type‐I aggregation‐induced emission luminogens (AIEgen) PSs (SAIE‐N3) on the cell membrane. Upon light irradiation, the membrane‐anchoring SAIE‐N3 could effectively generate type‐I reactive oxygen species (ROS) to induce gasdermin E (GSDME)‐mediated pyroptosis. In vivo experiments demonstrated that the bioorthogonal combination strategy of peptide and AIEgen PSs could significantly inhibit tumor growth, which is accompanied by CD8+ cytotoxic T cell infiltration. This work provides a novel self‐assembly peptide‐mediated bioorthogonal reaction strategy to bridge the supramolecular self‐assembly and AIE field through strain‐promoted azide‐alkyne cycloaddition (SPAAC) and elucidates that pure type‐I membrane‐anchoring PSs can be used for cancer therapy via GSDME‐mediated pyroptosis.
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