Artemisinin‐Directed Crystallization of an Iron‐Sulfasalazine Coordination Polymer for Acne Synergistic Phototherapy With Sustained Antibacterial and Pro‐Regenerative Effects

ABSTRACT Acne vulgaris, driven by Propionibacterium acnes infection, is poorly addressed by conventional phototherapy due to oxygen dependence, transient efficacy, and pro‐inflammatory side effects. Herein, we design a ternary coordination polymer (Fe‐SASP/ART) that overcomes these limitations while promoting keratinocyte proliferation. The first formed Fe‐sulfasalazine (SASP) precursors exhibit photothermal and photodynamic properties via ligand‐to‐metal charge transfer (LMCT). Artemisinin (ART) serves as coordinating ligands and structural inducers, transforming amorphous precursors into crystalline frameworks. The ART‐directed architecture enables oxygen‐independent carbon‐centered radical generation via Fe 2 + ‐catalyzed ART cleavage (Fe 2+ generated from LMCT), establishing a dual‐channel energy dissipation pathway that enhances photothermal and photodynamic performance. Notably, the iron‐mediated activation of ART establishes a self‐sustaining Fe 3+ /Fe 2+ redox cycle, driving prolonged radical production post‐irradiation for sustained antibacterial effect. The nanoplatform achieves 69.5% bactericidal efficacy against P. acnes upon NIR irradiation, suppresses pro‐inflammatory cytokines via SASP, and promotes keratinocyte proliferation (120.9% viability) through hormesis. Ex vivo studies confirm efficient follicular accumulation of the nanoplatform with controlled penetration depth. In mouse acne models, a single topical treatment with NIR irradiation elicits sustained lesion resolution over 5 days, with potent therapeutic efficacy, anti‐inflammatory effects, and excellent biocompatibility. This work offers a promising paradigm for safe and effective acne management.