Visible-Light-Harvesting Supramolecular Nanoassembly of Tetrathienylethene Tetrapyridinium/Cucurbit[7]uril for Bacterial Biofilm Eradication

Abstract

Bacterial biofilms act as a protective “umbrella” that significantly impairs antibiotic penetration, thereby hindering the complete eradication of infections. The clinical translation of organic photosensitizers for antimicrobial photodynamic therapy (aPDT) is critically hindered by their intrinsic self-aggregation in aqueous media, which severely compromises reactive oxygen species (ROS) generation and impedes penetration into dense bacterial biofilms. Herein, we report a visible-light-harvesting photosensitizer, tetrathienylethene tetrapyridinium chloride (TTC), and construct a supramolecular nanoassembly (TTC@CB[7]) with cucurbit[7]uril (CB[7]) via host–guest complexation. The CB[7] cavity selectively encapsulates the pyridinium moieties, imposing spatial confinement that disrupts detrimental π–π stacking and transforms micron-sized aggregates into uniform nanoscale colloids. This results in a reduction in hydrodynamic diameter from 1230 to 120 nm, a favorable shift in zeta potential from +0.67 mV to +30.9 mV, and a 1.3-fold increase in singlet oxygen quantum yield compared to free TTC. Consequently, under visible light, TTC@CB[7] exhibits a minimum inhibitory concentration (MIC) of 8 μg/mL against both Staphylococcus aureus and Pseudomonas aeruginosa. More importantly, its nanoscale size and enhanced positive charge facilitate deep penetration into the biofilm matrix, enabling complete eradication of mature biofilms with negligible dark cytotoxicity. This work presents a versatile supramolecular strategy that concurrently resolves aggregation and penetration barriers, paving the way for high-performance aPDT.