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A Targeting Singlet Oxygen Battery for Multidrug-Resistant Bacterial Deep-Tissue Infections |
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| Authors: | Yiwen Zhu Minzheng Gao Mengrui Su Yanzhe Shen Kai Zhang Bingran Yu Fu-Jian Xu |
| Institution: | 1. State Key Laboratory of Chemical Resource Engineering, Key Lab of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology, Ministry of Education), Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029 China
These authors contributed equally to this work. Contribution: Methodology (equal), Software (equal), Writing - original draft (lead);2. State Key Laboratory of Chemical Resource Engineering, Key Lab of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology, Ministry of Education), Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029 China These authors contributed equally to this work. Contribution: Methodology (equal), Software (equal), Writing - original draft (equal);3. State Key Laboratory of Chemical Resource Engineering, Key Lab of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology, Ministry of Education), Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029 China Contribution: Methodology (equal);4. State Key Laboratory of Chemical Resource Engineering, Key Lab of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology, Ministry of Education), Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029 China Contribution: Methodology (supporting);5. State Key Laboratory of Chemical Resource Engineering, Key Lab of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology, Ministry of Education), Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029 China Contribution: Data curation (lead);6. State Key Laboratory of Chemical Resource Engineering, Key Lab of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology, Ministry of Education), Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029 China |
| Abstract: | Traditional photodynamic therapy (PDT) is dependent on externally applied light and oxygen, and the depth of penetration of these factors can be insufficient for the treatment of deep infections. The short half-life and short diffusion distance of reactive oxygen species (ROS) also limit the antibacterial efficiency of PDT. Herein, we designed a targeting singlet oxygen delivery system, CARG-Py, for irradiation-free and oxygen-free PDT. This system was converted to the “singlet oxygen battery” CARG-1O2 and released singlet oxygen without external irradiation or oxygen. CARG-1O2 is composed of pyridones coupled to a targeting peptide that improves the utilization of singlet oxygen in deep multidrug-resistant bacterial infections. CARG-1O2 was shown to damage DNA, protein, and membranes by increasing the level of reactive oxygen inside bacteria; the attacking of multiple biomolecular sites caused the death of methicillin-resistant Staphylococcus aureus (MRSA). An in vivo study in a MRSA-infected mouse model of pneumonia demonstrated the potential of CARG-1O2 for the efficient treatment of deep infections. This work provides a new strategy to improve traditional PDT for irradiation- and oxygen-free treatment of deep infections while improving convenience of PDT. |
| Keywords: | Antibacterial Mechanism Deep-Tissue Infections Multidrug-Resistant Singlet Oxygen Battery Targeting Therapy |