Tetraphenylethene-glycocluster camouflaged lectin B-targeted nano-photosensitizer for antimicrobial photodynamic therapy of Pseudomonas aeruginosa and infected wound healing
摘要
The escalating prevalence of multidrug-resistant Pseudomonas aeruginosa (P. aeruginosa) infections necessitates novel antibacterial strategies. Here, we engineered lectin B (LecB)-targeted glyco-dots (TFP2F) via self-assembly of a photosensitizer (TFP2) possessing aggregation-induced reactive oxygen species (ROS) generation capability with fucose-modified tetraphenylethene glycoclusters (TPE-Fuc4), enabling P. aeruginosa-targeted antimicrobial photodynamic therapy and wound healing promotion. Three photosensitizers (TFP0–2) featuring an “A-D-A” electronic structure were synthesized, exhibiting broad absorption bands and near-infrared (NIR) fluorescence. Among these, TFP2 demonstrated superior Type-I/II ROS production (including ·OH, ·O2−, and 1O2), achieving potent phototoxicity against P. aeruginosa (MIC80 = 7.5 µM). Self-assembly with TPE-Fuc4 yielded glyco-dots TFP2F that facilitated LecB-mediated bacterial targeting, enhanced bacterial uptake, and significantly reduced the MIC80 to 2.5 µM against drug-resistant P. aeruginosa under light irradiation. In a murine P. aeruginosa-infected wound model, TFP2F treatment combined with light irradiation accelerated wound closure to <20% of the initial area by day 8 (vs. >40% in controls) and eliminated >95% of bacteria by day 2. This work presents a convenient strategy for constructing glyco-dots as a potent functionalized platform for precision, lectin-targeted antimicrobial photodynamic therapy.