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High-throughput Identification of Bacteria Repellent Polymers for Medical Devices
Published on: November 5, 2016
Polymersomes Eradicating Intracellular Bacteria
Federico Fenaroli1, James D Robertson2,3, Edoardo Scarpa4
1Department of Biosciences, University of Oslo, 0371 Oslo, Norway.
Abstract:
Mononuclear phagocytes such as monocytes, tissue-specific macrophages, and dendritic cells are primary actors in both innate and adaptive immunity. These professional phagocytes can be parasitized by intracellular bacteria, turning them from housekeepers to hiding places and favoring chronic and/or disseminated infection. One of the most infamous is the bacteria that cause tuberculosis (TB), which is the most pandemic and one of the deadliest diseases, with one-third of the world's population infected and an average of 1.8 million deaths/year worldwide. Here we demonstrate the effective targeting and intracellular delivery of antibiotics to infected macrophages both in vitro and in vivo, using pH-sensitive nanoscopic polymersomes made of PMPC-PDPA block copolymer. Polymersomes showed the ability to significantly enhance the efficacy of the antibiotics killing Mycobacterium bovis, Mycobacterium tuberculosis, and another established intracellular pathogen, Staphylococcus aureus. Moreover, they demonstrated to easily access TB-like granuloma tissues-one of the harshest environments to penetrate-in zebrafish models. We thus successfully exploited this targeting for the effective eradication of several intracellular bacteria, including M. tuberculosis, the etiological agent of human TB.
Insights
Nanoparticle polymersomes effectively deliver antibiotics inside infected macrophages, enhancing bacterial killing. This novel approach successfully targets tuberculosis granulomas and eradicates intracellular pathogens like Mycobacterium tuberculosis.
Area of Science:
- Immunology
- Infectious Diseases
- Nanomedicine
Background:
- Mononuclear phagocytes are crucial for immunity but can harbor intracellular bacteria, leading to chronic infections.
- Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a major global health threat, with infected macrophages serving as a reservoir.
- Effective treatment requires intracellular delivery of antibiotics to combat pathogens within host cells.
Purpose of the Study:
- To develop and evaluate pH-sensitive nanoscopic polymersomes for targeted intracellular antibiotic delivery.
- To assess the efficacy of polymersome-encapsulated antibiotics against Mycobacterium tuberculosis and Staphylococcus aureus in infected macrophages.
- To investigate the ability of polymersomes to penetrate TB-like granuloma tissues in vivo.
Main Methods:
- Utilized PMPC-PDPA block copolymer to create pH-sensitive nanoscopic polymersomes.
- Tested polymersome efficacy in vitro against Mycobacterium bovis, Mycobacterium tuberculosis, and Staphylococcus aureus in infected macrophages.
- Evaluated polymersome penetration into TB-like granuloma tissues in a zebrafish model.
Main Results:
- Polymersomes significantly enhanced the antibiotic efficacy in killing intracellular bacteria.
- Demonstrated successful targeting and intracellular delivery of antibiotics to infected macrophages.
- Showed polymersomes could effectively penetrate challenging TB-like granuloma tissues in vivo.
- Achieved eradication of Mycobacterium tuberculosis and other intracellular pathogens.
Conclusions:
- pH-sensitive nanoscopic polymersomes are a promising platform for targeted intracellular antibiotic delivery.
- This strategy effectively enhances the treatment of intracellular bacterial infections, including tuberculosis.
- The ability to penetrate granuloma tissues offers a new therapeutic avenue for difficult-to-treat infections.
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