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Evaluation of Antimicrobial Activities of Nanoparticles and Nanostructured Surfaces In Vitro
Published on: April 21, 2023
Nanoparticle-Like Scavenger Mediated by NIR/pH Stimulation for MRSA-Associated Infections
Xiangjun Chen1, Sai Zhang1, Yating Liu1
1School of Pharmacy, Shandong Medical and Pharmaceutical University, Yantai, People's Republic of China.
Abstract:
Methicillin-resistant Staphylococcus aureus (MRSA) infections represent a severe global clinical threat due to its multi-antibiotic resistance, abundant virulence factors, and complex pathogenic mechanisms. In the present study, hollow copper sulfide (CuS) nanoparticles (NPs) with a strong photothermal effect were employed as carriers for the loading of the NO-releasing bioactive molecule S-nitrosoglycine (GSNO). These NPs were also camouflaged with mouse red blood cell membranes (RBCMs) via extrusion to fabricate CuS-GSNO@RBCM NPs designed to effectively eliminate MRSA and its biofilms. Under 1064 nm near-infrared laser irradiation, CuS NPs had a mild photothermal effect, establishing an in situ catalytic platform that boosted reactive oxygen species (ROS) production. In the acidic infectious microenvironment, the release of copper ions induced GSNO to produce NO for reactive nitrogen species (RNS) generation. The ROS and RNS generated in situ by this system consumed endogenous MRSA glutathione, disrupting redox homeostasis, with the additional presence of copper ion-mediated copper death forming a multi-bactericidal network. The RBCMs also neutralized proteins secreted by MRSA to reduce lung cell injury. In vitro and in vivo experiments were employed to verify the MRSA-elimination efficacy of the proposed system, which offers an innovative nanotherapeutic strategy for the precise treatment of drug-resistant bacterial infections.
Insights
This study introduces novel nanoparticles that combine copper sulfide, a nitric oxide donor, and red blood cell membranes to combat antibiotic-resistant bacteria. This innovative approach effectively eliminates MRSA and its biofilms, offering a new treatment strategy.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Infectious Diseases
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant global health threat due to its resistance to multiple antibiotics.
- MRSA infections are characterized by numerous virulence factors and complex pathogenic pathways, complicating treatment strategies.
Purpose of the Study:
- To develop a novel nanotherapeutic system for effective elimination of MRSA and its biofilms.
- To utilize hollow copper sulfide nanoparticles (CuS NPs) as carriers for S-nitrosoglycine (GSNO) and camouflage them with red blood cell membranes (RBCMs).
Main Methods:
- Fabrication of CuS-GSNO@RBCM NPs for targeted delivery and enhanced therapeutic effects.
- Utilizing near-infrared laser irradiation to induce a photothermal effect from CuS NPs, generating reactive oxygen species (ROS).
- Exploiting the acidic microenvironment to release copper ions, triggering GSNO to produce nitric oxide (NO) and reactive nitrogen species (RNS).
Main Results:
- The combined ROS and RNS generation disrupted MRSA's redox homeostasis by consuming glutathione.
- Copper ions induced bacterial death, creating a multi-bactericidal network.
- Red blood cell membranes (RBCMs) mitigated lung cell injury by neutralizing MRSA-secreted proteins.
- In vitro and in vivo studies confirmed the system's efficacy against MRSA.
Conclusions:
- The CuS-GSNO@RBCM NP system presents an innovative nanotherapeutic strategy for treating drug-resistant bacterial infections.
- This approach offers a multi-pronged attack against MRSA, involving photothermal therapy, ROS/RNS generation, and copper ion toxicity.
- The RBCM camouflage enhances safety by reducing host cell damage.
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