High-performance lung-targeted bio-responsive platform for severe colistin-resistant bacterial pneumonia therapy.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38404643.
- Also identified by DOI 10.1016/j.bioactmat.2024.02.017 and PMC identifier 10885821.
- Licence recorded as CC BY-NC-ND.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
Abstract
Polymyxins are the last line of defense against multidrug-resistant (MDR) Gram-negative bacterial infections. However, this last resort has been threatened by the emergence of superbugs carrying the mobile colistin resistance gene-1 <i>(mcr-1).</i> Given the high concentration of matrix metalloproteinase 3 (MMP-3) in bacterial pneumonia, limited plasma accumulation of colistin (CST) in the lung, and potential toxicity of ionic silver (Ag<sup>+</sup>), we designed a feasible clinical transformation platform, an MMP-3 high-performance lung-targeted bio-responsive delivery system, which we named "CST&Ag@CNMS". This system exhibited excellent lung-targeting ability (>80% in lungs), MMP-3 bio-responsive release property (95% release on demand), and synergistic bactericidal activity <i>in vitro</i> (2-4-fold minimum inhibitory concentration reduction). In the <i>mcr-1</i><sup><i>+</i></sup> CST-resistant murine pneumonia model, treatment with CST&Ag@CNMS improved survival rates (70% vs. 20%), reduced bacteria burden (2-3 log colony-forming unit [CFU]/g tissue), and considerably mitigated inflammatory response. In this study, CST&Ag@CNMS performed better than the combination of free CST and AgNO<sub>3</sub>. We also demonstrated the superior biosafety and biodegradability of CST&Ag@CNMS both <i>in vitro</i> and <i>in vivo</i>. These findings indicate the clinical translational potential of CST&Ag@CNMS for the treatment of lung infections caused by CST-resistant bacteria carrying <i>mcr-1</i>.