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

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 (C-MB) was synthesized through quaternization, and its structure, interface properties, photophysical properties and antibacterial photodynamic properties were studied. The results showed that C-MB could reduce 4.27 log CFU and 4.8 log CFU for and under irradiation of light at 660 nm, higher than the parent methylene blue. Through a spectroscopic study on photosensitizer adsorption over the bacterial surface, C-MB can be accumulated with higher concentration, and the photo-active monomer content is 73% and 70% over and , 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 C-MB adsorbed over bacterial surfaces, planar packing inhibition and electrostatic repulsion could contribute to lower C-MB aggregation, which provides an useful reference for the structural design of high-efficiency photosensitizers.