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Updated: May 30, 2025
Author Spotlight: Exploring the Antibacterial Effects of Zinc Oxide Nanoparticles in Overcoming Antibiotic Resistance
Published on: September 27, 2024
Metal Ion and Antibiotic Co-loaded Nanoparticles for Combating Methicillin-Rresistant Staphylococcus aureus-Induced
Hui Lv1,2,3,4, Ming Yang2,3,4, Yusheng Yang3
1Department of Emergency and trauma orthopedics, the 958th Hospital of Chinese People's Liberation Army, Army Medical University (Third Military Medical University), Chongqing 400023, China.
Abstract:
Methicillin-resistant Staphylococcus aureus (MRSA) causes osteomyelitis (OM), which seriously threatens public health due to its antimicrobial resistance. To increase the sensitivity of antibiotics and eradicate intracellular bacteria, a Zn2+ and vancomycin (Van) codelivered nanotherapeutic (named Man-Zn2+/Van NPs) was fabricated and characterized via mannose (Man) modification. Man-Zn2+/Van NPs exhibit significant inhibitory activity against extra- and intracellular MRSA and obviously decrease the minimum inhibitory concentration of Van. Man-Zn2+/Van NPs can be easily internalized by MRSA-infected macrophages and significantly accumulated in infected bone via Man-mediated targeting. In vivo experiments in a mouse OM model verified that Man-Zn2+/Van NPs significantly reduce the extra- and intracellular MRSA burden, improve gait patterns, increase bone mass, and decrease inflammatory cytokine expression. The antibacterial mechanism of Man-Zn2+/Van NPs includes destruction of the MRSA membrane, degeneration of intracellular proteins and DNA, inhibition of MRSA glycolysis, and intervention in the energy metabolism of bacteria. Overall, this metal-antibiotic nanotherapeutics strategy provides new insight for combating extra- and intracellular infections caused by MRSA-induced OM.
Insights
A novel nanotherapeutic combining zinc and vancomycin effectively targets and eliminates both extracellular and intracellular methicillin-resistant Staphylococcus aureus (MRSA) in osteomyelitis models. This approach enhances antibiotic efficacy and offers a promising strategy against resistant bacterial infections.
Area of Science:
- Nanomedicine
- Infectious Diseases
- Biomaterials
Background:
- Osteomyelitis (OM) caused by methicillin-resistant Staphylococcus aureus (MRSA) poses a significant public health challenge due to antimicrobial resistance.
- Effective eradication of both extracellular and intracellular MRSA is crucial for successful OM treatment.
Purpose of the Study:
- To develop and characterize a novel zinc and vancomycin co-delivered nanotherapeutic (Man-Zn2+/Van NPs) for enhanced MRSA osteomyelitis treatment.
- To evaluate the efficacy of Man-Zn2+/Van NPs in targeting and eliminating MRSA, both in vitro and in vivo.
Main Methods:
- Fabrication and characterization of mannose-modified zinc and vancomycin co-delivered nanoparticles (Man-Zn2+/Van NPs).
- In vitro assessment of antibacterial activity against extracellular and intracellular MRSA, including minimum inhibitory concentration (MIC) determination.
- In vivo evaluation in a mouse osteomyelitis model to assess therapeutic efficacy, bone healing, and inflammatory response.
Main Results:
- Man-Zn2+/Van NPs demonstrated significant inhibitory activity against extra- and intracellular MRSA, reducing vancomycin's MIC.
- The nanoparticles showed efficient internalization by macrophages and targeted accumulation in infected bone tissue.
- In vivo studies confirmed a significant reduction in MRSA burden, improved gait, increased bone mass, and decreased inflammatory markers.
Conclusions:
- Mannose-mediated targeted delivery of zinc and vancomycin nanoparticles offers a potent strategy against MRSA osteomyelitis.
- This nanotherapeutic approach effectively combats both extracellular and intracellular MRSA, enhancing antibiotic sensitivity and promoting bone healing.
- Metal-antibiotic nanotherapeutics represent a promising avenue for addressing challenging resistant bacterial infections.
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