Enzyme-coated mesoporous silica nanoparticles as efficient antibacterial agents in vivo
1Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, No. 11 Beiyitiao, Zhongguancun, Beijing, China.
Abstract:
Despite the fact that pathogenic infections are widely treated by antibiotics in the clinic nowadays, the increasing risk of multidrug-resistance associated with abuse of antibiotics is becoming a major concern in global public health. The increased death toll caused by pathogenic bacterial infection calls for effective antibiotic alternatives. Lysozyme-coated mesoporous silica nanoparticles (MSNs⊂Lys) are reported as antibacterial agents that exhibit efficient antibacterial activity both in vitro and in vivo with low cytotoxicity and negligible hemolytic side effect. The Lys corona provides multivalent interaction between MSNs⊂Lys and bacterial walls and consequently raises the local concentration of Lys on the surface of cell walls, which promotes hydrolysis of peptidoglycans and increases membrane-perturbation abilities. The minimal inhibition concentration (MIC) of MSNs⊂Lys is fivefold lower than that of free Lys in vitro. The antibacterial efficacy of MSNs⊂Lys is evaluated in vivo by using an intestine-infected mouse model. Experimental results indicate that the number of bacteria surviving in the colon is three orders of magnitude lower than in the untreated group. These natural antibacterial enzyme-modified nanoparticles open up a new avenue for design and synthesis of next-generation antibacterial agents as alternatives to antibiotics.
Insights
Lysozyme-coated mesoporous silica nanoparticles (MSNs⊂Lys) show potent antibacterial activity, outperforming free lysozyme. These nanoparticles offer a promising alternative to antibiotics for combating drug-resistant infections.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Infectious Disease Research
Background:
- Antibiotic resistance is a growing global health crisis, necessitating novel therapeutic strategies.
- Pathogenic bacterial infections contribute to increased mortality rates worldwide.
- Traditional antibiotics face challenges due to widespread multidrug resistance.
Purpose of the Study:
- To investigate the antibacterial efficacy of lysozyme-coated mesoporous silica nanoparticles (MSNs⊂Lys) as an alternative to conventional antibiotics.
- To evaluate the in vitro and in vivo performance of MSNs⊂Lys.
- To explore the mechanism of action of MSNs⊂Lys in disrupting bacterial cell walls.
Main Methods:
- Synthesis and characterization of lysozyme-coated mesoporous silica nanoparticles (MSNs⊂Lys).
- In vitro assessment of antibacterial activity, including determination of minimal inhibition concentration (MIC).
- In vivo evaluation of MSNs⊂Lys efficacy in a mouse model of intestinal bacterial infection.
Main Results:
- MSNs⊂Lys demonstrated significantly enhanced antibacterial activity compared to free lysozyme, with a fivefold lower MIC.
- The nanoparticles exhibited low cytotoxicity and negligible hemolytic effects.
- In vivo studies showed a three-logarithmic reduction in surviving bacteria in the colon of treated mice compared to controls.
Conclusions:
- Lysozyme-modified nanoparticles represent a novel class of antibacterial agents with superior efficacy.
- MSNs⊂Lys offer a promising platform for developing next-generation antibacterial therapies to combat multidrug-resistant pathogens.
- This approach provides a new avenue for designing effective alternatives to traditional antibiotics.
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