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Updated: May 20, 2025
Establishing a Porcine Ex Vivo Cornea Model for Studying Drug Treatments against Bacterial Keratitis
Published on: May 12, 2020
Synchronous Sterilization and Immunoreaction Termination for Corneal Transparency Protection in Treating Pseudomonas
Siyuan Qian1,2, Xuan Wang1,2,3, Yishun Guo1,2
1National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, 325000, China.
Abstract:
In the treatment of infectious keratitis, therapeutic strategies often prioritize enhancing bactericidal efficacy. However, endotoxins released from Gram-negative bacteria cause inflammatory reaction, leading to corneal structural damage and scar formation. Given that polymyxin B (PMB) can bind and neutralize lipopolysaccharide (LPS), this study employs large-pore mesoporous silica nanoparticles (lMSNs) grafted with PMB as carriers for cationic antibacterial carbon quantum dots (CQDs) to prepare CQD@lMSN-PMB, which enables synchronous sterilization and endotoxin neutralization. In the acidic infectious microenvironment, the accelerated release of CQDs eliminates 99.88% bacteria within 2 h, effectively substituting immune mediated sterilization. Notably, CQD@lMSN-PMB exhibits exceptional LPS neutralization performance (2.22 µg LPS/mg CQD@lMSN-PMB) due to its high specific surface area. In an infectious keratitis model, inflammation subsides significantly within the first day of CQD@lMSN-PMB intervention and is completely resolved by day 3. By day 2, interleukin-1β, interleukin-6 and tumor necrosis factor-α in CQD@lMSN-PMB group decrease by 86.99%, 91.15%, and 77.56%, respectively, compared to the CQDs-only sterilization group. Ultimately, corneal integrity and transparency are preserved, with suppressed expressions of fibrosis-related factors including matrix metalloproteinase 9, transforming growth factor-β and α-smooth muscle actin. Therefore, this synchronous sterilization and endotoxin neutralization strategy outperforms monotherapy strategies focused solely on sterilization or endotoxin neutralization.
Insights
This study developed a novel nanoparticle that kills bacteria and neutralizes harmful endotoxins simultaneously, effectively treating infectious keratitis and preserving corneal health.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Ophthalmology
Background:
- Infectious keratitis treatment often focuses on bacterial killing, but endotoxins from Gram-negative bacteria cause inflammation and corneal damage.
- Polymyxin B (PMB) neutralizes lipopolysaccharide (LPS), a key endotoxin, but requires effective delivery.
Purpose of the Study:
- To develop a dual-action therapeutic agent for infectious keratitis that combines bacterial sterilization and endotoxin neutralization.
- To evaluate the efficacy of PMB-grafted mesoporous silica nanoparticles loaded with carbon quantum dots (CQD@lMSN-PMB) in an infectious keratitis model.
Main Methods:
- Synthesized CQD@lMSN-PMB nanoparticles for synchronous sterilization and LPS neutralization.
- Assessed antibacterial efficacy and LPS binding capacity in vitro.
- Investigated therapeutic effects in an infectious keratitis animal model, monitoring inflammation and corneal healing.
Main Results:
- CQD@lMSN-PMB achieved 99.88% bacterial elimination within 2 hours in an acidic environment.
- Demonstrated high LPS neutralization capacity (2.22 µg LPS/mg CQD@lMSN-PMB).
- Significantly reduced inflammatory markers (IL-1β, IL-6, TNF-α) and fibrosis factors, preserving corneal integrity and transparency.
Conclusions:
- The developed CQD@lMSN-PMB nanoparticles offer a superior therapeutic strategy for infectious keratitis by combining sterilization and endotoxin neutralization.
- This dual-action approach effectively mitigates inflammation and promotes corneal healing, outperforming monotherapy strategies.
