A pH-Gated Functionalized Hollow Mesoporous Silica Delivery System for Photodynamic Sterilization in Staphylococcus aureus Biofilm.

Multidrug-resistant bacteria are increasing, particularly those embedded in microbial biofilm. These bacteria account for most microbial infections in humans. Traditional antibiotic treatment has low efficiency in sterilization of biofilm-associated pathogens, and thus the development of new approaches is highly desired. In this study, amino-modified hollow mesoporous silica nanoparticles (AHMSN) were synthesized and used as the carrier to load natural photosensitizer curcumin (Cur). Then glutaraldehyde (GA) and polyethyleneimine (PEI) were used to seal the porous structure of AHMSN by the Schiff base reaction, forming positively charged AHMSN@GA@PEI@Cur. The Cur delivery system can smoothly diffuse into the negatively charged biofilm of Staphylococcus aureus (S. aureus). Then Cur can be released to the biofilm after the pH-gated cleavage of the Schiff base bond in the slightly acidic environment of the biofilm. After the release of the photosensitizer, the biofilm was irradiated by the blue LED light at a wavelength of 450 nm and a power of 37.4 mV/cm2 for 5 min. Compared with the control group, the number of viable bacteria in the biofilm was reduced by 98.20%. Therefore, the constructed pH-gated photosensitizer delivery system can efficiently target biofilm-associated pathogens and be used for photodynamic sterilization, without the production of antibiotic resistance.