The One-Stop Integrated Nanoagent Based on Photothermal Therapy for Deep Infection Healing and Inflammation Inhibition

Chronic wounds caused by bacterial infections are a major challenge in medical fields. The hypoxia condition extremely induces reactive oxygen species (ROS) generation and upregulates the expression of hypoxia-inducible factor, both of which can increase the pro-inflammatory M1 subtype macrophages production while reducing the anti-inflammatory M2 subtype macrophages. Besides, bacteria-formed biofilms can hinder the penetration of therapeutic agents. Encouraged by natural motors automatically executing tasks, hypothesized that supplying sufficient oxygen (O2) would simultaneously drive therapeutic agent movement, rescue the hypoxic microenvironment, and disrupt the vicious cycle of inflammation. Here, small organic molecule-based nanoparticles (2TT-mC6B@Cu5.4O NPs) that possess high photothermal conversion efficiency and enzymatic activities are developed, including superoxide dismutase-, catalase-, and glutathione peroxidase-like activity. 2TT-mC6B@Cu5.4O NPs exhibit superior ROS-scavenging and O2 production abilities that synergistically relieve inflammation, alleviate hypoxia conditions, and promote their deep penetration in chronic wound tissues. Transcriptome analysis further demonstrates that 2TT-mC6B@Cu5.4O NPs inhibit biological activities inside bacteria. Furthermore, in vivo experiments prove that 2TT-mC6B@Cu5.4O NPs-based hyperthermia can effectively eliminate bacteria in biofilms to promote wound healing. The 2TT-mC6B@Cu5.4O NPs are designed and fabricated to eliminate bacterial biofilms and facilitate the MRSA-infected abscess wound healing. The ROS-scavenging, O2-producing, and regulation of macrophage polarization mechanisms based on multiple enzymatic activities and the photothermal property are revealed. Herein, a reasonable antibacterial and anti-inflammation approach against infected wounds and a reference for other hypoxia-relative inflammatory diseases is demonstrated.image