EngineeredHouttuynia cordata-derived exosome-like nanoparticles as a dual-targeting platform for eradicating

Zhi Gong1, Ruixue Zhang1, Gongming Shi2

  • 1School of Pharmaceutical Sciences, Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chongqing University, Chongqing 401331, China.

Insights

A novel dual-targeting nanoparticle system effectively delivers rifampicin to combat intracellular methicillin-resistant Staphylococcus aureus (MRSA) infections. This approach overcomes antibiotic access barriers, showing promise for treating persistent bacterial reservoirs.

Area of Science:

  • Nanomedicine
  • Infectious Diseases
  • Microbiology

Background:

  • Intracellular infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are difficult to treat due to limited antibiotic penetration into macrophage reservoirs.
  • Conventional therapies struggle to reach bacteria residing within host cells, leading to persistent infections.

Purpose of the Study:

  • To develop and evaluate a dual-targeting nanoparticle system for enhanced delivery of rifampicin to intracellular MRSA.
  • To overcome physiological barriers limiting conventional antibiotic efficacy against intracellular pathogens.

Main Methods:

  • Engineered Houttuynia cordata-derived exosome-like nanoparticles (HELNs) encapsulating rifampicin (Rif) and functionalized with mannose and vancomycin (Rif@HELNs-MV).
  • Investigated mannose receptor-mediated endocytosis for macrophage targeting and vancomycin-mediated binding to intracellular MRSA.
  • Characterized nanoparticle morphology, Rif loading capacity, cellular uptake, and antibacterial efficacy in murine infection models.

Main Results:

  • Rif@HELNs-MV nanoparticles exhibited spherical morphology and high rifampicin loading capacity (18.3 ± 2.1%).
  • Demonstrated enhanced cellular uptake and precise targeting of intracellular MRSA.
  • Showed superior antibacterial efficacy in murine peritonitis and muscle infection models, significantly reducing bacterial loads with good biocompatibility.

Conclusions:

  • The dual-targeting strategy using Rif@HELNs-MV effectively delivers antibiotics to intracellular MRSA reservoirs.
  • This nanomedicine approach shows significant potential for treating persistent intracellular bacterial infections by overcoming conventional therapeutic limitations.

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