Multitarget aminated fullerene hydrogels ameliorate psoriasis by scavenging ROS, inhibiting keratinocyte hyperproliferation, and reshaping the inflammatory microenvironment

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.