HAase/GSH dual-responsive mesoporous organosilica nanoparticles for synergistic photodynamic/photothermal/pharmacological antibacterial therapy

Mesoporous organosilica nanoparticles (MONs) are promising drug carriers with excellent biocompatibility and biodegradability. In the context of the bacterial infection microenvironment, a hyaluronidase (HAase)/glutathione (GSH) dual-responsive degradable nanoplatform based on MON (ICG/CIP@MON@PEI-HA) has been developed for the multimodal treatment of bacterial infection. In this work, ciprofloxacin (CIP) and indocyanine green (ICG) are physically adsorbed into the MON, polyethyleneimine (PEI) is electrostatically adsorbed onto the MON surface, and hyaluronic acid (HA) is grafted onto the amino groups of PEI via the amide bonds. The overexpression of HAase at bacterial infection sites enables HA shell degradation, and positively charged PEI is exposed, which facilitates nanoparticle binding to negatively charged bacteria. Also, owing to the protonation of amine groups, PEI is swelled in the acidic environment of bacterial infection, which favours drug release. Subsequently, overexpressed GSH breaks the disulfide bonds in the MON, triggering structural degradation that inhibits carrier accumulation and accelerates drug release even further. According to in vitro antibacterial evaluations, the antibacterial effect can be enhanced to 100% when phototherapy and pharmaceutical therapy are combined. In vitro cytotoxicity assays have demonstrated that ICG/CIP@MON@PEI-HA possesses excellent biocompatibility. Therefore, this study offers a potential approach for developing biodegradable nanoplatforms for the combined treatment of bacterial infection.