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The One-Stop Integrated Nanoagent Based on Photothermal Therapy for Deep Infection Healing and Inflammation
Wentao Wang1, Yumeng Gao2, Wang Xu2
1College of Science, Nanjing Forestry University, Nanjing, 210037, China.
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@Cu5.4 O NPs) that possess high photothermal conversion efficiency and enzymatic activities are developed, including superoxide dismutase-, catalase-, and glutathione peroxidase-like activity. 2TT-mC6B@Cu5.4 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@Cu5.4 O NPs-based hyperthermia can effectively eliminate bacteria in biofilms to promote wound healing.
Insights
New nanoparticles deliver oxygen to chronic wounds, reducing inflammation and killing bacteria. This approach combats hypoxia and biofilms, promoting effective wound healing.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Wound Healing
Background:
- Chronic wounds are complicated by bacterial infections and hypoxia.
- Hypoxia promotes inflammation by increasing M1 macrophages and decreasing M2 macrophages.
- Bacterial biofilms impede therapeutic agent penetration and treatment efficacy.
Purpose of the Study:
- To develop novel nanoparticles for oxygen delivery to chronic wounds.
- To investigate the nanoparticles' ability to alleviate hypoxia and inflammation.
- To assess the nanoparticles' efficacy in combating bacterial biofilms and promoting wound healing.
Main Methods:
- Synthesis of small organic molecule-based nanoparticles (2TT-mC6B@Cu5.4O NPs) with photothermal and enzymatic activities.
- Evaluation of ROS-scavenging and oxygen production capabilities.
- In vitro transcriptome analysis to assess effects on bacterial activity.
- In vivo experiments using nanoparticle-based hyperthermia for biofilm eradication.
Main Results:
- 2TT-mC6B@Cu5.4O NPs effectively scavenge ROS and produce oxygen, alleviating hypoxia and inflammation.
- Nanoparticles demonstrated superior penetration into chronic wound tissues.
- Transcriptome analysis revealed inhibition of bacterial biological activities.
- In vivo hyperthermia with NPs eradicated bacteria in biofilms, promoting wound healing.
Conclusions:
- 2TT-mC6B@Cu5.4O NPs offer a promising therapeutic strategy for chronic wounds.
- Oxygen-releasing nanoparticles can reverse hypoxia-induced inflammation and combat bacterial infections.
- This approach effectively disrupts biofilms and accelerates wound healing through combined hyperthermia and antimicrobial action.
