Reactive oxygen species-sensitive thioketal-linked mesoporous silica nanoparticles as drug carrier for effective antibacterial activity

Mesoporous silica nanoparticles (MSNs) carrying gatekeepers that are stimuli-responsive are widely investigated for the controlled delivery of drug at target sites. In this study, thioketal (TK) functionalized methoxy poly(ethylene glycol) (mPEG-TK) as ROS-responsive gatekeeper is used to modify MSNs and leads to a reactive oxygen species (ROS)-responsive delivery for antibacterial drug. Vancomycin (Van) was taken as the antibacterial drug and then physically encapsulated into the surface amino functionalized MSNs (N-MSNs). Subsequently, mPEG-TK was surface immobilized. Van loaded N-MSNs with surface modification of mPEG-TK (Van-mPEG-TK-MSNs) presented approximately 21% release of Van in a physiological environment in 36 h. With H₂O₂ increasing in the medium, the release rate of Van from Van-mPEG-TK-MSNs was significantly up-regulated following gatekeepers' disintegration. When Van-mPEG-TK-MSNs was applied in vivo, the infected site was fully cleared after 14 days and the tissue was free of infection. On the whole, the mentioned results suggested that Van-mPEG-TK-MSNs could act as a potential antimicrobial. This study can broaden MSNs' applications and advance the development of novel antibacterial agents.