| Affiliation: | 1. Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Sanhang Science & Technology Building No. 45th, Gaoxin South 9th Road, Nanshan District, Guangdong, 518063 P. R. China;2. Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Sanhang Science & Technology Building No. 45th, Gaoxin South 9th Road, Nanshan District, Guangdong, 518063 P. R. China Xi'an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, 127 West Youyi Road, Beilin District, Xi'an, 710072 P. R. China;3. Xi'an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, 127 West Youyi Road, Beilin District, Xi'an, 710072 P. R. China;4. Frontiers Science Center for Flexible Electronics (FSCFE), Xi'an Institute of Flexible Electronics (IFE) and Xi'an Institute of Biomedical Materials & Engineering (IBME), Northwestern Polytechnical University, 127 West Youyi Road, Beilin District, Xi'an, 710072 P. R. China;5. Key Laboratory of Biorheological Science and Technology, Ministry of Education College of Bioengineering, Chongqing University, 174 Shazheng Street, Shapingba District, Chongqing, 400044 P. R. China |
| Abstract: | The use of non-antibiotic strategies to combat refractory drug-resistant bacterial infections, especially biofilms and accompanying inflammation, has recently aroused widespread interest. Herein, a photo-therapeutic nanocomposite with bio-responsive oxygen (O2) self-supplying is introduced by integrating manganese dioxide (MnO2) nanozymes onto photosensitizer (indocyanine green, ICG)-loaded mesoporous polydopamine nanoparticles (MPDA), namely MI-MPDA NPs. MI-MPDA can activate O2 generation in the infection microenvironment, thereby effectively alleviating biofilm hypoxia. Under near-infrared light (NIR) irradiation, continuous O2 supplying further boosts the level of singlet oxygen (1O2), enabling robust biofilm elimination through O2-potentiated photodynamic/photothermal therapy. Interestingly, MI-MPDA down-regulates the factor expression of inflammatory signaling pathways through MnO2-mediated reactive oxygen species scavenging, which ameliorates the inflammatory condition. Meanwhile, O2 supplying prevents the M1-phenotype switch of macrophages from the overexpression of hypoxia-inducible factor-1α (HIF-1α), thereby prompting macrophage reprogramming toward pro-regenerative M2-phenotype. In the mouse models of subcutaneous implant-associated infection caused by methicillin-resistant Staphylococcus aureus (MRSA) biofilms and burn infection caused by Pseudomonas aeruginosa biofilms, NIR-irradiated MI-MPDA not only effectively eliminates the formed biofilms, but also alleviates the oxidative stress and accompanying inflammation, and drives the cascade reaction of immunomodulation-wound healing. Overall, this O2-potentiated photo-therapeutic strategy provides a reliable tool for combating biofilm infections and inflammation from drug-resistant bacteria. |
