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Formulation and candidacidal activity of magnetic nanoparticles coated with cathelicidin LL-37 and ceragenin CSA-13
Katarzyna Niemirowicz1, Bonita Durnaś2, Grażyna Tokajuk3
1Department of Microbiological and Nanobiomedical Engineering, Medical University of Bialystok, 15-222, Białystok, Poland.
Abstract:
Fungal infections caused by Candida spp. represent an emerging problem during treatment of immunocompromised patients and those hospitalized with serious principal diseases. The ever-growing number of fungal strains exhibiting drug resistance necessitates the development of novel antimicrobial therapies including those based on membrane-permeabilizing agents and nanomaterials as drug carriers. In this study, the fungicidal activities of LL-37 peptide, ceragenin CSA-13 and its magnetic derivatives (MNP@LL-37, MNP@CSA-13) against laboratory and clinical strains of C. albicans, C. glabrata and C. tropicalis were evaluated. These experiments confirm the high anti-fungal activity of these well-characterized agents mediated by their interaction with the fungal membrane and demonstrate elevated activity following immobilization of LL-37 and CSA-13 on the surface of magnetic nanoparticles (MNPs). Furthermore, MNP-based nanosystems are resistant to inhibitory factors present in body fluids and effectively inhibit formation of fungal biofilm. Simultaneously, synthesized nanostructures maintain immunomodulatory properties, described previously for free LL-37 peptide and CSA-13 substrate and they do not interfere with the proliferation and viability of osteoblasts, confirming their high biocompatibility.
Insights
Novel magnetic nanoparticles carrying antifungal peptides LL-37 and ceragenin CSA-13 show potent activity against drug-resistant Candida strains. These biocompatible nanostructures inhibit biofilm formation and retain immunomodulatory properties.
Area of Science:
- Antimicrobial research
- Nanotechnology
- Mycology
Background:
- Fungal infections, particularly by Candida species, pose a significant threat to immunocompromised and hospitalized patients.
- Increasing drug resistance in Candida strains necessitates the development of new antifungal therapies.
- Antimicrobial peptides and nanomaterials offer promising avenues for novel treatment strategies.
Purpose of the Study:
- To evaluate the fungicidal activity of LL-37 peptide and ceragenin CSA-13, and their magnetic nanoparticle (MNP) conjugates (MNP@LL-37, MNP@CSA-13).
- To assess the efficacy of these agents against laboratory and clinical strains of Candida albicans, Candida glabrata, and Candida tropicalis.
- To investigate the impact of MNP immobilization on the antifungal activity, biofilm inhibition, and biocompatibility of LL-37 and CSA-13.
Main Methods:
- Synthesis and characterization of magnetic nanoparticle conjugates (MNP@LL-37, MNP@CSA-13).
- In vitro evaluation of fungicidal activity against multiple Candida species using standard microbiological assays.
- Assessment of biofilm inhibition and immunomodulatory properties of the synthesized nanostructures.
- Biocompatibility testing using osteoblast cell lines.
Main Results:
- LL-37 peptide and ceragenin CSA-13 demonstrated significant fungicidal activity against tested Candida strains.
- Immobilization onto magnetic nanoparticles (MNPs) enhanced the antifungal efficacy of both LL-37 and CSA-13.
- MNP-based nanosystems effectively inhibited Candida biofilm formation and resisted inhibitory factors in body fluids.
- The synthesized nanostructures maintained immunomodulatory properties and exhibited high biocompatibility with osteoblasts.
Conclusions:
- Magnetic nanoparticle-conjugated LL-37 and CSA-13 represent a potent and biocompatible strategy for combating drug-resistant Candida infections.
- These MNP-based systems offer advantages in terms of enhanced activity, biofilm control, and stability in biological environments.
- The findings support the potential of these novel nanostructures as therapeutic agents for invasive fungal infections.
