Stimuli-responsive mesoporous silica nanoplatforms for smart antibacterial therapies: From single to combination strategies.

The demand for new antibacterial therapies is urgent and crucial in the clinical setting because of the growing degree of antibiotic resistance and the limits of conventional antibacterial therapies. Stimuli- responsive nanoplatforms, are sensitive to endogenous or exogenous stimulus (pH, temperature, light, and magnetic fields, etc.) which activate cargo release locally and on-demand, hold great potential in developing next generation personalized precision medicine. For instance, pH-sensitive nanoplatforms can selectively release antibacterial agents in the acidic environment of infection sites. To achieve the stimuli-responsive delivery, mesoporous silica nanoplatforms (MSNs) have demonstrated as prospective candidates for efficient cargo loading and controlled release through strategies such as tunable pore engineering, versatile surface modification/coating, and tailored framework composition. Furthermore, aiming for more precise delivery of MSNs, current research interests are increasingly shifting from single-stimuli antibacterial strategy to integrated strategy that combine multiple-stimulus. In this review, we briefly discuss the microenvironment of bacterial infections and provide a comprehensive summary of current stimuli-responsive strategies, and associated materials design principles of stimuli-responsive mesoporous silica-based smart nanoplatforms (SRMSNs). Additionally, integrative antibacterial strategies with synergistic effects, combining chemodynamic, photodynamic, photothermal, sonodynamic and gas therapies, have also been elaborated. Present research advances and limitations of SRMSNs-based antibacterial therapies, such as limited biodegradability and potential cytotoxicity, have been overviewed with future outlooks presented. This review aims to inspire and guide future research in developing novel antibacterial strategies with integrative solutions.