Hyaluronic acid-engineered infection-responsive liposomes achieve biofilm penetration and synergistic photothermal-photodynamic antibacterial therapy

Bacterial infections, particularly those caused by drug-resistant strains and biofilm-associated wounds, pose serious challenges in clinical treatment. Although phototherapy is a promising Antibacterial approach, conventional photosensitizers suffer from poor stability, low photothermal conversion efficiency, and limited biofilm penetration. Herein, we developed an infection-responsive hyaluronic acid-modified cationic liposomal platform (HA@ICG@Lip) for synergistic photodynamic and photothermal Antibacterial therapy. Elevated hyaluronidase (HAase) levels in infected tissues specifically degrade the outer HA layer, triggering enzyme-responsive deshielding to expose the positively charged liposomal core, which enhances Bacterial adhesion and deep biofilm penetration. Upon near-infrared irradiation, indocyanine green (ICG) generates Reactive Oxygen Species and localized heat, inducing Bacterial membrane disruption and biofilm disintegration. Moreover, ICG forms J-aggregates within the liposomal matrix, improving near-infrared absorption and photothermal conversion efficiency. In vivo, HA@ICG@Lip combined with 808 nm LED irradiation effectively eradicated mixed-species biofilm infections and accelerated wound healing. This study provides a polysaccharide-based, infection-responsive phototherapeutic nanoplatform with potential for treating biofilm-associated infections.