摘要
Antimicrobial photodynamic therapy (aPDT) offers a promising alternative to conventional antibiotics, yet its application to Gram-negative bacteria remains limited by the poor membrane association and rapid diffusion of most photosensitizers. Here, we report a protein-mediated strategy that overcomes this intrinsic barrier by nano-delivering the porphyrin-binding translocator protein (TSPO) to the outer membrane of Escherichia coli. TSPO was reconstituted into lipid nanodiscs and transferred to bacterial membranes without genetic manipulation of the host cells. Membrane-localized TSPO retained high-affinity binding to protoporphyrin IX (PpIX), enabling stable photosensitizer anchoring at the bacterial surface. Upon light irradiation, the TSPO-PpIX complex generated localized reactive oxygen species, resulting in pronounced photodynamic inhibition of bacterial growth in both wild-type and lipopolysaccharide-deficient E. coli strains. Complementary in vivo assays leveraging endogenous PpIX biosynthesis further confirmed that TSPO-mediated photosensitizer localization is sufficient to drive photodynamic inactivation. Together, these results establish nano-delivered TSPO as a versatile protein-based platform for enhancing aPDT against Gram-negative bacteria and provide a generalizable framework for overcoming membrane-associated resistance in antimicrobial phototherapy. © 2026 The Chemical Society Located in Taipei and Wiley-VCH GmbH.
