Lysosomal zinc nanomodulation blocks macrophage pyroptosis for counteracting atherosclerosis progression.

ABSTRACT: Macrophage pyroptosis has been identified as a critical pathological mechanism in inflammation-related atherosclerosis (AS). In this work, we have demonstrated that Zn²⁺ features the strongest anti-inflammatory performance by screening 10 representative metal ions, and the MTC1 agonists can trigger lysosomal Zn²⁺ release and inhibit pyroptosis in macrophages. Based on these findings, we further engineered a mucolipin TRP channel 1 (MTC1)-related therapeutic nanoplatform for endogenously triggering lysosomal zinc release to curb inflammation and block macrophage pyroptosis. This nanoplatform consists of mesoporous silica nanoparticles to deliver MTC1 agonists and carbon nanodots, which could synergistically exert antiatherosclerotic effect by scavenging toxic reactive

SUBMITTER: Hu R 

PROVIDER: S-EPMC12189970 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature