Amphiphilic di-cationic methylene blue for improving antibacterial photodynamic efficiency through high accumulation and low aggregation on bacterial cell surfaces

RSC Adv. 2022 Dec 20;13(1):239-250. doi: 10.1039/d2ra06484g. eCollection 2022 Dec 19.

Abstract

The aggregation state of photosensitizers on the surface of bacterial cells is an important scientific problem for antibacterial photodynamic therapy (APDT). High accumulation and high photoactive state maintenance of photosensitizers are the prerequisite of high APDT efficiency. In this study, an amphiphilic di-cationic methylene blue photosensitizer (C12-MB) was synthesized through quaternization, and its structure, interface properties, photophysical properties and antibacterial photodynamic properties were studied. The results showed that C12-MB could reduce 4.27 log10 CFU and 4.8 log10 CFU for P. aeruginosa and S. aureus under irradiation of light at 660 nm, higher than the parent methylene blue. Through a spectroscopic study on photosensitizer adsorption over the bacterial surface, C12-MB can be accumulated with higher concentration, and the photo-active monomer content is 73% and 70% over P. aeruginosa and S. aureus, higher than those of methylene blue: 25% and 49%, respectively. The higher content of non-aggregated photo-active monomer could contribute to higher antibacterial photodynamic efficiency. For C12-MB adsorbed over bacterial surfaces, planar packing inhibition and electrostatic repulsion could contribute to lower C12-MB aggregation, which provides an useful reference for the structural design of high-efficiency photosensitizers.