Nitric Oxide‐Assisted Photodynamic Therapy for Enhanced Penetration and Hypoxic Bacterial Biofilm Elimination

Abstract The presence of a biofilm matrix barrier and hypoxic microenvironment within the biofilm significantly impedes the efficacy of photodynamic therapy for bacterial biofilm infections. Herein, a phototherapeutic nanoagent with type‐I photodynamic behavior and nitric oxide (NO) release performance is reported for overcoming biofilm‐associated infectious diseases. Sodium nitroprusside (SNP), a NO donor, is loaded onto amino‐modified mesoporous silica nanoparticles (MSN) to form MSN@SNP NPs. The resulting nanoparticles are further modified with a porphyrin‐based metal–organic framework (Ti‐TCPP MOF) to obtain MSN@MOF/SNP NPs (MMS NPs) for phototherapeutic applications. In the hypoxia biofilm microenvironment, the MMS NPs release NO to enhance the biofilm permeability and induce the generation of hydroxyl radical (•OH) and superoxide anion radical (O 2 •− ) via Type‐I photodynamic pathway under laser irradiation. Subsequently, the biofilm‐associated infections are effectively eliminated through reactive oxygen species (ROS) and NO gas synergistic therapy. In addition, NO also stimulates collagen deposition and promotes angiogenesis in vivo. Therefore, the MMS NPs efficiently treat biofilm‐related infections, providing an alternative approach to combat biofilm‐associated infectious diseases.