biostudies-literatureDai XNational Natural Science Foundation of China2500221https://www.ebi.ac.uk/biostudies/studies/S-EPMC12412604biostudies-literatureUnknown5(9)Atherosclerosis (AS) is a significant contributor to cardiovascular events. Recent studies have demonstrated that ferroptosis of foam cells is a significant driver of AS. Nevertheless, insights into the precise antiferroptosis therapies remain limited. Here, a multifunctional theranostic nanoplatform is engineered by conjugating folate-modified polydopamine (PDA) nanoparticles (NPs) with L-arginine (FPLG) to inhibit ferroptosis of foam cells. In vitro studies demonstrate that FPLG NPs effectively attenuate ferroptosis in oxidized low-density lipoprotein (ox-LDL)-stimulated macrophages by scavenging reactive oxygen species, upregulating GPX4 and NRF2 activity, and regulating lipid metabolism. In vivo, FPLG NPs exhibit preferential accumulation in atherosclerotic plaques via folate receptorsSmall sciencePositron Emission Tomography/Computed Tomography Imaging-Guided Polydopamine Nanoparticles Attenuate Foam Cell Ferroptosis for Targeted Antiatherosclerotic Therapy.PMC124126048244101982271992Liu XYang GSheng JQi JLu GLu JWang FZhang LWang ZDai XXu YZheng TfalsePositron Emission Tomography/Computed Tomography Imaging-Guided Polydopamine Nanoparticles Attenuate Foam Cell Ferroptosis for Targeted Antiatherosclerotic Therapy.Atherosclerosis (AS) is a significant contributor to cardiovascular events. Recent studies have demonstrated that ferroptosis of foam cells is a significant driver of AS. Nevertheless, insights into the precise antiferroptosis therapies remain limited. Here, a multifunctional theranostic nanoplatform is engineered by conjugating folate-modified polydopamine (PDA) nanoparticles (NPs) with L-arginine (FPLG) to inhibit ferroptosis of foam cells. In vitro studies demonstrate that FPLG NPs effectively attenuate ferroptosis in oxidized low-density lipoprotein (ox-LDL)-stimulated macrophages by scavenging reactive oxygen species, upregulating GPX4 and NRF2 activity, and regulating lipid metabolism. In vivo, FPLG NPs exhibit preferential accumulation in atherosclerotic plaques via folate receptors2025-01-01T00:00:00Z2025 Sep2026-06-01T07:55:23.989Z2026-04-08T10:40:54.334ZS-EPMC124126044091739410.1002/smsc.202500221