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 Fe² ⁺-catalyzed ART cleavage (Fe²⁺ 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 Fe³⁺/Fe²⁺ 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.