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Antibacterial Activity of Zinc-Doped Hydroxyapatite and Vancomycin-Loaded Gelatin Nanoparticles against Intracellular
Lizzy A B Cuypers1, Leonie de Boer2, Rong Wang1
1Department of Dentistry-Regenerative Biomaterials, Research Institute Medical Innovations, Radboud University Medical Center, Philips van Leydenlaan 25, 6525 EX Nijmegen, The Netherlands.
Abstract:
Treating bone infections with common antibiotics is challenging, since pathogens like Staphylococcus aureus can reside inside macrophages. To target these intracellular bacteria, we have proposed nanoparticles (NPs) as drug carriers. This study aims to investigate the efficacy of hydroxyapatite and gelatin NPs, selected in view of their bone mimicry and potential for targeted delivery, as carriers for the antibacterial agents zinc and vancomycin. Therefore, two distinct NPs are fabricated: zinc-doped hydroxyapatite (ZnHA) and vancomycin-loaded gelatin (VGel) NPs. The NPs are characterized based on morphology, size, chemical composition, cellular internalization, and intracellular bactericidal efficacy. Specifically, the intracellular bactericidal efficacy is tested using a validated coculture model of human THP-1 derived macrophages and phagocytosed S. aureus bacteria. Scanning electron microscopy (SEM) and Fourier transform-infrared spectroscopy (FTIR) results show that the spherical NPs are synthesized successfully. These NPs are internalized by THP-1 cells and show >75% colocalization with lysosomes without compromising the viability of the THP-1 cells. Both ZnHA and VGel NPs substantially reduce the intracellular survival of S. aureus compared to the direct addition of dissolved zinc and vancomycin. Concluding, our NPs are highly effective drug delivery vehicles to kill intracellular S. aureus, which stress the potential of these NPs for future clinical translation.
Insights
Novel nanoparticles effectively deliver antibacterial agents zinc and vancomycin to kill intracellular Staphylococcus aureus within macrophages, offering a promising strategy for bone infection treatment.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Infectious Diseases
Background:
- Treating bone infections is difficult due to intracellular bacteria like Staphylococcus aureus residing within macrophages.
- Conventional antibiotics struggle to reach and eliminate these intracellular pathogens effectively.
- Nanoparticles (NPs) offer a potential solution for targeted intracellular drug delivery.
Purpose of the Study:
- To investigate the efficacy of hydroxyapatite and gelatin NPs as drug carriers for antibacterial agents.
- To evaluate zinc-doped hydroxyapatite (ZnHA) and vancomycin-loaded gelatin (VGel) NPs for treating intracellular S. aureus infections.
- To assess the potential of these bone-mimicking NPs for clinical translation in bone infection therapy.
Main Methods:
- Fabrication and characterization of ZnHA and VGel NPs using SEM and FTIR.
- Assessment of NP cellular internalization and lysosomal colocalization in THP-1 macrophages.
- Evaluation of intracellular bactericidal efficacy against S. aureus within a macrophage coculture model.
Main Results:
- Spherical ZnHA and VGel NPs were successfully synthesized and characterized.
- NPs were efficiently internalized by THP-1 cells, localizing with lysosomes (>75%) without toxicity.
- Both ZnHA and VGel NPs significantly reduced intracellular S. aureus survival compared to free drugs.
Conclusions:
- Developed ZnHA and VGel NPs are effective drug delivery vehicles for targeting intracellular S. aureus.
- These NPs demonstrate significant potential for treating bone infections caused by intracellular bacteria.
- The bone-mimicking nature and efficacy highlight the clinical translatability of these nanocarriers.
