Mild photothermal-driven nanorobots for infected wound healing through effective photodynamic therapy and wound microenvironment remodeling

Abstract

Biofilms provide a stable microenvironment that not only fosters bacterial survival but also poses great challenges for bacterial eradication. Photodynamic therapy (PDT) is a broad-spectrum antibacterial method with great potential for treating superficial biofilm-infected diseases. However, the protective barrier and hypoxic microenvironment within biofilms severely impede the efficacy of PDT. Herein, we developed photothermal-driven nanorobots (denoted as Ce6-ACPBNRs), capable of efficient locomotion and PDT under mild irradiation conditions, to penetrate and disrupt biofilms, remodel the wound microenvironment, and thus accelerate the healing process. The nanorobots consisted of bowl-shaped polydopamine nanoparticles, whose surfaces were sequentially modified with α-amylase, catalase, and chlorin e6 (Ce6). Due to their distinctive bowl-shaped structure, the nanorobots can effectively propel within various biological media upon exposure to mild laser irradiation. Assisted by α-amylase, the self-propelled nanorobots can achieve a 3-fold increase in penetration depth within biofilms in 10 min. Simultaneously, they can alleviate hypoxia by decomposing in situ H₂O₂ into O₂, thereby significantly enhancing the efficacy of PDT against deep-seated bacteria and achieving a biofilm degradation efficiency of 91%. Moreover, the Ce6-ACPBNRs can rapidly internalize into macrophages and modulate their phenotype, thereby enhancing their pathogen phagocytosis and tissue repair capabilities. These synergistic effects enable them to exhibit enhanced therapeutic efficacy in wound healing within a bacteria-infected wound mouse model. Therefore, this study presents a promising strategy for combating bacterial biofilm-associated infections.