In Situ Conversion of Atherosclerotic Plaques’ Iron into Nanotheranostics
Wenqi Pan, Sihui Shao, Xinyue Cao, Xinyue Dai, Yi Zheng, Jingyun Cheng, Wei Feng, Rong Wu, Yu Chen
Abstract
The presence of a substantial necrotic core in atherosclerotic plaques markedly heightens the risk of rupture, a consequence of elevated iron levels that exacerbate oxidative stress and lipid peroxidation, thereby sustaining a detrimental cycle of ferroptosis and inflammation. Concurrently targeting both ferroptosis and inflammation is crucial for the effective treatment of vulnerable plaques. In this study, we introduce gallium hexacyanoferrate nanoabsorption catalysts (GaHCF NACs) designed to disrupt this pathological cycle. GaHCF NACs function as highly efficient iron chelators with robust antiferroptosis properties. Through in situ capture of iron within atherosclerotic plaques, these catalysts enhance reactive oxygen species scavenging, initiating an amplified therapeutic response. GaHCF NACs significantly advance plaque regression, stabilization, and vascular functional recovery by inhibiting MAPK13 (p38-δ MAPK) signaling, a key mediator of inflammation and cell death. Importantly, the in situ iron capture process generates a detectable photoacoustic signal, offering a notable diagnostic advantage that allows real-time monitoring of plague status. This multifunctional nanocatalytic platform in situ transforms toxic iron within atherosclerotic plaques into both a therapeutic and diagnostic agent, adapting dynamically to the microenvironment and representing a promising strategy for reducing plaque vulnerability and preventing rupture.