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

Abstract

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@Cu_5.4 O NPs) that possess high photothermal conversion efficiency and enzymatic activities are developed, including superoxide dismutase-, catalase-, and glutathione peroxidase-like activity. 2TT-mC6B@Cu_5.4 O 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@Cu_5.4 O NPs-based hyperthermia can effectively eliminate bacteria in biofilms to promote wound healing.