Psoriasis is a chronic inflammatory skin disease driven by oxidative stress, keratinocyte hyperproliferation, and immune dysregulation. Conventional single-target therapies frequently result in incomplete remission and disease relapse. Here, we designed amino-functionalized fullerene hydrogels (TAPC@CB/TPPC@CB) that coordinately restore oxidative and inflammatory homeostasis via a multitarget mechanism. These hydrogels normalize keratinocyte proliferation by upregulating the cell-cycle inhibitor Cdkn1b, inducing G0/G1 arrest, and eliminating excessive reactive oxygen species (ROS). They also promote macrophage polarization toward the anti-inflammatory M2 phenotype and downregulate stress-related and proinflammatory proteins, thereby inhibiting the NF-κB/IL-23/Th17 axis and restoring the inflammatory microenvironment. In vivo, topical TAPC@CB significantly reduced macrophage and T-cell infiltration, alleviated inflammation, and lowered recurrence risk. This study establishes amino-fullerene-based hydrogels as a single-agent, multipathway nanotherapeutic strategy for effective psoriasis treatment and relapse prevention.

Intimate immune hyperactivation and subsequent vascular endothelial dysfunction are involved in the main pathophysiology of heart failure (HF). However, existing treatments through immunomodulation and endothelial protection for HF are not fully developed. In this study, we introduced PEGylated C₆₀ fullerene nanoparticles (FNPs-PEG2000, FPs) as a two-pronged strategy to mitigate myocardial injury in mice with HF via superior immunomodulation combined with endothelial barrier restoration. The FPs exhibit prolonged systemic circulation, potent reactive oxygen species (ROS) scavenging capacity, and biocompatibility. Mechanistically, FPs suppress M1-type macrophage polarization, inhibit macrophage pyroptosis via the caspase-1/GSDMD pathway blockade, and restore endothelial barrier integrity by stabilizing junctional proteins. In a murine post-infarction HF model, FPs significantly improve cardiac function (left ventricular ejection fraction: 34.1% vs. 19.2% in HF controls), reduce fibrosis, and normalize pathological markers. Single-cell transcriptomics further reveal FPs-driven immunomodulation (66.48% neutrophil reduction and 78.98% endothelial restoration) and pro-angiogenic gene activation. Collectively, FPs demonstrate a multimodal therapeutic mechanism by disrupting ROS-inflammation crosstalk, preserving endothelial barrier integrity, and promoting cardiac repair, thus offering a promising translational candidate for HF management.