From bio-interfacial association to sustained delivery: a lipophilicity-tuned aggregation-induced emission photosensitizer hydrogel for infected wound therapy.

The antimicrobial activity of cationic aggregation-induced emission photosensitizers (AIE-PSs) is strongly influenced by their interactions with microbial interfaces. Here, we examined how cationic valency and lipophilicity affect interfacial association and antimicrobial performance, and whether hydrogel confinement can further regulate local delivery. Four triphenylamine-pyridinium AIE-PSs with different charge states and terminal substituents were compared for lipophilicity, aggregation behavior, reactive oxygen species generation, microbial interfacial association, and antimicrobial activity against Escherichia coli, Staphylococcus aureus, and Candida albicans. TPA-PY-C6 showed the highest lipophilicity (LogP = 1.894) and the strongest association with the C. albicans interface, reaching 91.77% adsorption and shifting the fungal zeta potential from -26.21 to -16.2 mV. Its minimum inhibitory concentrations for 90% growth inhibition (MIC90) were 10, 2, and 5 μM against E. coli, S. aureus, and C. albicans, respectively. Incorporation of TPA-PY-C6 into a genipin-crosslinked gelatin/hyaluronic acid hydrogel reduced burst release and sustained local delivery. In separate bacterial- and fungal-infected wound models, TPA-PY-C6@Gel reduced microbial burden and improved wound repair. These results show that antimicrobial performance can be tuned at two complementary levels: molecular amphiphilicity governs microbial interfacial association, whereas the hydrogel network regulates local retention and release.