Dual-mode antibacterial photodynamic and photothermal therapy via indocyanine green-loaded bismuth selenide spherical sponge

Bacterial infections, exacerbated by rising antibiotic resistance, urgently demand innovative antimicrobial strategies. However, conventional indocyanine green (ICG)-based phototherapies are limited by poor photostability, rapid degradation, and nonspecific distribution, which hinder their clinical translation. In this study, we developed a multifunctional nanoplatform integrating photodynamic therapy (PDT) and photothermal therapy (PTT), using hollow bismuth selenide (Bi 2 Se 3 , BS) nano-spherical sponges to encapsulate ICG. The resulting BS/ICG (BSI) hybrid leverages the high surface area and photothermal properties of BS to enhance ICG loading capacity (82.28 % ± 3.42 %) and enable controlled release under near-infrared (NIR) irradiation. Upon 808 nm light activation, the BSI system generates abundant reactive oxygen species (ROS) and induces localized hyperthermia, synergistically disrupting bacterial membranes and biofilms. In vitro experiments demonstrated that the bactericidal efficiency of this platform achieved 99.01 % ± 0.37 % against Staphylococcus aureus and 99.10 % ± 0.28 % against Escherichia coli within just 5 min. Mechanistic studies revealed that ROS-induced oxidative damage and thermal lysis act synergistically on bacterial membrane components, while biofilm formation is inhibited through downregulation of biofilm-associated genes, effectively reducing the risk of bacterial resistance. In an infected mouse wound model, the BSI system significantly accelerated wound healing, promoted neovascularization, suppressed inflammatory responses, and enhanced collagen deposition. Both in vitro and in vivo biocompatibility assessments confirmed the excellent biosafety of the system. This work introduces a promising dual-modal nanotherapeutic platform based on PDT/PTT, offering a valuable alternative for combating multidrug-resistant infections and promoting tissue regeneration.