Flexible nanoplatform facilitates antibacterial phototherapy by simultaneously enhancing photosensitizer permeation and relieving hypoxia in bacterial biofilms

Antimicrobial phototherapy has gained recognition as a promising approach for addressing bacterial biofilms, however, its effectiveness is often impeded by the robust physical and chemical defenses of the biofilms. Traditional antibacterial nanoplatforms face challenges in breaching the extracellular polymeric substances barrier to efficiently deliver photosensitizers deep into biofilms. Moreover, the prevalent hypoxia within biofilms restricts the success of oxygen-reliant phototherapy. In this study, we engineered a soft mesoporous organosilica nanoplatform (SMONs) by incorporating polyethylene glycol (PEG), catalase (CAT), and indocyanine green (ICG), forming SMONs-PEG-CAT-ICG (SPCI). We compared the antimicrobial efficacy of SPCI with more rigid nanoplatforms. Our results demonstrated that unique flexible mechanical properties of SPCI enable it to navigate through biofilm barriers, markedly enhancing ICG penetration in methicillin-resistant Staphylococcus aureus (MRSA) biofilms. Notably, in a murine subcutaneous MRSA biofilm infection model, SPCI showed superior biofilm penetration and pharmacokinetic benefits over its rigid counterparts. The embedded catalase in SPCI effectively converts excess H