TWEAK-Conjugated Selenoviologen as a Novel Photosensitizer for Selective Wound Accumulation and Synergistic Healing of Drug-Resistant Bacterial Infections

• • SeV-Tp generates high levels of reactive oxygen species under visible light, achieving potent antibacterial activity against both Gram-positive and Gram-negative bacteria, including antibiotic-resistant strains, with no measurable resistance development. • • SeV-Tp selectively binds to Fn14-overexpressing cells in wounds, leading to preferential accumulation in wound tissue and minimal adverse effects, addressing the bottleneck of diffuse photosensitizer distribution. • • The conjugate activates the MAPK pathway, upregulating key tissue-remodeling factors such as MMP2 and EGFR, a biological effect absent with free SeV, resulting in superior wound closure, collagen deposition, and angiogenesis in animal studies. • • In a mouse model of antibiotic-resistant Pseudomonas aeruginosa-infected wound, SeV-Tp significantly accelerated healing by reducing bacterial burden, modulating the immune microenvironment, promoting collagen deposition, and stimulating hair follicle regeneration.