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.

Functional fullerene derivatives exhibit special inhibitory effects on tumor progress and metastasis via diverse tumor microenvironment regulations, while the elusive molecular mechanisms hinder their clinical transformation. Herein, it is initially revealed that nanosize aminated fullerene (C₇₀-EDA) can activate autophagic flux, induce G0/G1 cell cycle arrest to abrogate cancer cell proliferation, and significantly inhibit tumor growth in vivo. Mechanismly, C₇₀-EDA promotes the expression of cathepsin D involved in autophagic activation via post-transcriptional regulation, attributing to the interaction with a panel of RNA binding proteins. The accumulation of cathepsin D induces the autophagic degradation of cyclin D1, which arouses G0/G1 phase arrest. This work unveils the fantastic anti-tumor activity of aminated fullerene, elucidates the molecular mechanism, and provides a new strategy for the antineoplastic drug development on functional fullerenes.