Redox-responsive degradation of antimicrobials with programmable drug release for enhanced antibacterial activity

The global crisis of antibiotic resistance has impelled the exigency to develop more effective drug delivery systems for the treatment of bacterial infection. The development of possessing high biocompatibility and targeted delivery of antimicrobials remains a persisting challenge. For programmable release of efficient antimicrobials in infection sites to enhance antibacterial activity, herein, we fabricated diselenide-bridged mesoporous organosilica nanoparticle-supported silver nanoparticles (Ag NPs) with high drug-loading capacity for the co-delivery of tobramycin (TOB) within one drug delivery system (Ag-MON@TOB (Se)). The resultant Ag-MON@TOB (Se) exhibited favorable biocompatibility due to its high stability in the physiological condition. Notably, such Ag-MON@TOB (Se) manifested a programmable structural destabilization to trigger sequential drug release in response to the oxidative stimuli within the bacterial infection microenvironment. In contradistinction to the oxidation-stable disulfide bond moieties within the framework of the nanocarrier (Ag-MON@TOB (S)), the Ag-MON@TOB (Se) with its programmed drug release behavior augmented prominent antibacterial therapy both in vitro and in vivo . This work represents a promising strategy for programmable drug release by harnessing a responsive degradable vehicle to enhance the treatment of bacterial infection. • Ag-MONs@TOB exhibits rapid degradation in the infected REDOX microenvironment, enabling simultaneous release of antimicrobials in time and space. Subsequently, the accelerated release of silver ions caused bacterial membrane damage, enhanced the permeability of TOB, and synergistic bactericidal activity. • Ag-MONs@TOB contains reduced chemical bonds that are specifically released during high levels of oxidative stress in bacterial infections. • Ag-MONs@TOB has good biocompatibility and ensures the biological safety and clinical application possibility at large doses.