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<p>Bacterial pneumonia is the most common infectious disease with high morbidity and short-term mortality. The key to the treatment of bacterial pneumonia is rapid clearance of the pathogen and effective control of the inflammatory response. In this study, a disulfide-bonded hydroxyl-rich hyperbranched polyaminoglycosides of tobramycin (SS-HPT) was synthesized. SS-HPT could be electrostatically complexed with plasmid DNA (pDNA) encoding heme oxygenase-1 (pHO-1) to form complexes nanoparticles (HPT/HO), which successfully achieved efficient intracellular delivery of pHO-1. HPT/HO exhibited broad-spectrum antibacterial properties, good cytotoxicity, highly efficient reactive oxygen species (ROS) scavenging capacity, and effective anti-inflammatory properties. In addition, HPT/HO exhibited good bacteriostatic properties and effective transfection in the lungs of Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA)-infected pneumonia mice, alleviated the cytokine storm and oxidative stress levels in the lungs, suppressed the over-activated inflammatory response, avoided the generation of lung injury, and improved the survival rate of mice. This study provided an antimicrobial gene carrier that provides a reliable target and effective method for the clinical treatment of MRSA pneumonia.</p>

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Construct nucleic acid delivery carriers with excellent antibacterial capabilities for the treatment of bacterial MRSA-induced lung inflammation

  • 期刊论文

  • 发表日期：

    2025年4月22日

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  • Zhen Li,
  • Chenyu Dong,
  • Shaobin Wu,
  • Zihui Liu,
  • Keyang Li,
  • Tong Li,
  • Shasha He,
  • Nuo Dong,
  • Kai Hao,
  • Huayu Tian

摘要

Bacterial pneumonia is the most common infectious disease with high morbidity and short-term mortality. The key to the treatment of bacterial pneumonia is rapid clearance of the pathogen and effective control of the inflammatory response. In this study, a disulfide-bonded hydroxyl-rich hyperbranched polyaminoglycosides of tobramycin (SS-HPT) was synthesized. SS-HPT could be electrostatically complexed with plasmid DNA (pDNA) encoding heme oxygenase-1 (pHO-1) to form complexes nanoparticles (HPT/HO), which successfully achieved efficient intracellular delivery of pHO-1. HPT/HO exhibited broad-spectrum antibacterial properties, good cytotoxicity, highly efficient reactive oxygen species (ROS) scavenging capacity, and effective anti-inflammatory properties. In addition, HPT/HO exhibited good bacteriostatic properties and effective transfection in the lungs of Methicillin-resistant Staphylococcus aureus (MRSA)-infected pneumonia mice, alleviated the cytokine storm and oxidative stress levels in the lungs, suppressed the over-activated inflammatory response, avoided the generation of lung injury, and improved the survival rate of mice. This study provided an antimicrobial gene carrier that provides a reliable target and effective method for the clinical treatment of MRSA pneumonia.