Multifunctional mesoporous superparamagnetic Iron oxide-based nanocomposites for synergistic Photothermal/Fenton therapy in the treatment of acne vulgaris.

Acne vulgaris is a common chronic inflammatory dermatosis primarily mediated by the dysregulated proliferation of Cutibacterium acnes (C. acnes). The current therapeutic efficacy is severely compromised by the widespread antibiotic resistance of C. acnes. To overcome this limitation, we designed mesoporous superparamagnetic iron oxide (MSPIONs) nanoparticles through an innovative one-step bubble-templated approach, and then the PMS (phase change material modified MSPIONs) loaded with CuO and Quercetin (Que) nanocomposites (PMS/CuO/Que) were synthesized. PMS/CuO/Que. exhibited remarkable biocompatibility (>90 % cell viability at 200 μg/mL), near-infrared (NIR) -triggered release properties, and broad-spectrum antimicrobial performance. Mechanistic investigations demonstrated that PMS/CuO/Que. releases Fe2+/Cu+ ions under acidic acne microenvironments (pH ∼5.0), initiating intense intrabacterial Fenton/Fenton-like reactions that generate cytotoxic hydroxyl radicals (•OH). PMS/CuO/Que. synergized with photothermally induced membrane disruption, this cascade causes nucleic acid leakage and biofilm complete eradication, achieving potent bactericidal effects. In murine acne models, PMS/CuO/Que. markedly attenuated proinflammatory cytokines versus PBS controls (33 % reduction in interleukin-6 (IL-6), 46 % in tumor necrosis factor-alpha (TNF-α), 51 % in monocyte chemoattractant protein-1 (MCP-1)). Lesion thickness decreased by 75 % with nearly-complete symptom resolution and restored cutaneous homeostasis on the ninth day. These compelling results establish PMS/CuO/Que. as a breakthrough therapeutic strategy for acne vulgaris, integrating potent antibacterial action, skin regenerative capacity, and enhanced biosafety.