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Macrophage-targeted amphiphilic peptide nanocarrier for intracellular MRSA infection therapy

Zaipeng Chen1, Yuling Wu2, Zhiqiang Nie1

  • 1State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, School of Pharmaceutical Sciences, Guizhou Medical University, No. 6 Ankang Avenue, Guian New District, Guiyang, Guizhou 561113, China.

Colloids and Surfaces. B, Biointerfaces
|September 23, 2025
PubMed

Insights

This study introduces RFP@TVYV, a novel nanomicelle drug delivery system that enhances macrophage uptake and delivers rifampin (RFP) to eradicate intracellular bacteria like MRSA effectively.

Area of Science:

  • Nanotechnology and Drug Delivery
  • Infectious Diseases
  • Bacteriology

Background:

  • Intracellular bacterial infections present challenges due to poor cellular entry and low antibiotic effectiveness within host cells.
  • Existing treatments struggle with antibiotic sequestration in cellular compartments, limiting efficacy against intracellular pathogens.

Purpose of the Study:

  • To design and evaluate an amphiphilic peptide nanomicelle system (RFP@TVYV) for enhanced macrophage targeting and intracellular bacteria eradication.
  • To achieve sequential targeting of macrophages and controlled release of rifampin (RFP) and a cell-penetrating peptide (TAT) for improved antibacterial activity.

Main Methods:

  • Synthesis and characterization of RFP@TVYV nanomicelles via hydrogen bonding and hydrophobic interactions.
  • Evaluation of macrophage internalization using flow cytometry (FC) and immunofluorescence (IF).
  • Assessment of antibacterial activity against Staphylococcus aureus in vitro and in vivo, including cytotoxicity studies.

Main Results:

  • RFP@TVYV demonstrated stable nanomicelle formation and significantly enhanced macrophage uptake.
  • The system effectively released rifampin (RFP) intracellularly, showing potent activity against Staphylococcus aureus.
  • In vitro and in vivo studies confirmed a substantial reduction in intracellular bacterial load with minimal cytotoxicity compared to free RFP.

Conclusions:

  • RFP@TVYV is a promising drug delivery platform for overcoming challenges in treating intracellular bacterial infections.
  • The nanoplatform shows significant potential for combating drug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA).
Keywords:
Amphiphilic peptide nanocarrierCathepsin B-responsive releaseIntracellular bacterial infectionMacrophage targetingMethicillin-resistant Staphylococcus aureus (MRSA)

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