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Preparation of Agar Bead Embedded Mycobacterium abscessus to Inoculate Immunocompetent Mice Intratracheally
Published on: April 25, 2025
AgNP-Containing Niosomes Functionalized with Fucoidan Potentiated the Intracellular Killing of Mycobacterium
Nereyda Niño-Martínez1,2, Kayla Audreyartha1, Kaitlyn Cheung1
1Faculty of Medicine, Division of Infectious Diseases, University of British Columbia, Vancouver, BC V6H3Z6, Canada.
Abstract:
Intracellular pathogens represent a challenge for therapy because the antibiotics used need to diffuse into the cytoplasm to target the pathogens. The situation is more complicated in the mycobacteria family because members of this family infect and multiply within macrophages, the cells responsible for clearing microorganisms in the body. In addition, mycobacteria members are enclosed inside pathogen-containing vesicles or phagosomes. The treatments of these pathogens are aggravated when these pathogens acquire resistance to antibiotic molecules. As a result, new antimicrobial alternatives are needed. Niosomes are vesicles composed of cholesterol and nonionic surfactants that can be used for antibiotic encapsulation and delivery. The current study developed a systematic formulation of niosomes to determine the best option for niosome functionalizing for precise delivery to the intracellular pathogen Mycobacterium abscessus. Silver nanoparticles (AgNPs) were synthesized using gallic acid as an antibacterial agent. Then, niosomes were prepared and characterized, following the encapsulation of AgNPs functionalized with a single-chain antibody screened against the cell wall glycopeptidolipid of Mycobacterium abscessus. For a precise delivery of the cargo into macrophages, the niosomes were also functionalized with the polysaccharide fucoidan, taken specifically by the scavenger receptor class A expressed on the surface of macrophages. Results of the study showed a steady decrease in the intracellular pathogen load after 48 h post-infection. In conclusion, this system could be developed into a platform to target other types of intracellular pathogens and as an option for antimicrobial therapy.
Insights
New niosome formulations carrying silver nanoparticles precisely target intracellular Mycobacterium abscessus. This novel drug delivery system effectively reduces bacterial load within macrophages, offering a promising antimicrobial therapy alternative.
Area of Science:
- Nanotechnology
- Microbiology
- Drug Delivery
Background:
- Intracellular pathogens like Mycobacterium abscessus pose treatment challenges due to their location within host cells and phagosomes.
- Mycobacterial infections are complicated by antibiotic resistance and the need for drugs to penetrate host cells.
- Niosomes offer a potential solution for encapsulating and delivering antimicrobial agents to intracellular targets.
Purpose of the Study:
- To systematically formulate and optimize niosomes for targeted delivery of antimicrobial agents to Mycobacterium abscessus.
- To functionalize niosomes with specific targeting moieties for enhanced uptake by macrophages.
- To evaluate the efficacy of functionalized niosomes loaded with silver nanoparticles against intracellular Mycobacterium abscessus.
Main Methods:
- Synthesis of silver nanoparticles (AgNPs) using gallic acid as an antibacterial agent.
- Preparation and characterization of niosomes encapsulating AgNPs.
- Functionalization of niosomes with a single-chain antibody against M. abscessus cell wall and fucoidan for macrophage targeting.
- In vitro assessment of the reduction in intracellular pathogen load post-treatment.
Main Results:
- Successfully synthesized and characterized AgNPs and functionalized niosomes.
- Demonstrated effective encapsulation of AgNPs within niosomes.
- Observed a significant decrease in intracellular Mycobacterium abscessus load at 48 hours post-infection.
- Validated the targeted delivery of niosomes to macrophages via scavenger receptor class A.
Conclusions:
- Developed a novel niosome-based platform for targeted delivery of silver nanoparticles to intracellular Mycobacterium abscessus.
- The functionalized niosome system shows potential as an effective antimicrobial therapy.
- This approach could be extended to target other intracellular pathogens.
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