A TAT Peptide-Functionalized Liposome Delivery Phage System (TAT-Lip@PHM) for an Enhanced Eradication of

Kaixin Liu1, Xin Lu2, Xudong Guo1

  • 1Chinese PLA Center for Disease Control and Prevention, Beijing 100071, China.

Pharmaceutics
|June 27, 2025
PubMed

Insights

This study developed a novel phage delivery system, TAT-Lip@PHM, to combat intracellular MRSA infections. The system efficiently delivers bacteriophages into cells, achieving a 94.05% eradication rate with minimal toxicity, offering a promising alternative to antibiotics.

Area of Science:

  • Microbiology
  • Biotechnology
  • Drug Delivery Systems

Background:

  • Intracellular bacteria like Methicillin-resistant Staphylococcus aureus (MRSA) cause persistent infections.
  • Antibiotic resistance and poor cellular penetration limit treatment efficacy against intracellular MRSA.
  • Bacteriophages offer a potential alternative but face challenges in cellular delivery and stability.

Purpose of the Study:

  • To develop and evaluate a novel bacteriophage-based delivery system for treating intracellular MRSA infections.
  • To enhance phage efficacy and overcome limitations of traditional antibiotic therapies.

Main Methods:

  • Isolation of a novel MRSA bacteriophage (vB_SauS_PHM).
  • Encapsulation of the bacteriophage within TAT peptide-functionalized liposomes using microfluidics and SEC, creating TAT-Lip@PHM.
  • Assessment of phage encapsulation rate, cellular uptake efficiency, intracellular MRSA eradication rate, and mammalian cell cytotoxicity.

Main Results:

  • The TAT-Lip@PHM system demonstrated a 20.3% phage encapsulation rate and over 90% cell entry efficiency within 8 hours.
  • A 24-hour treatment with 300 μg/mL TAT-Lip@PHM achieved a 94.05% eradication rate of intracellular MRSA.
  • The system exhibited high mammalian cell viability (>85%) after 24 hours, indicating low cytotoxicity.

Conclusions:

  • The TAT-Lip@PHM system effectively delivers bacteriophages into host cells.
  • This novel system shows significant potential for treating intracellular MRSA infections with high efficacy and low toxicity.
  • Provides a valuable technical framework for developing phage-based therapies against intracellular bacterial pathogens.

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