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Thermoresponsive antioxidant metal-free carbon nanodot hydrogel: An effective therapeutic approach for ocular surface
Mei Yang1, Xin Chen1,2, Zhongxing Chen1
1Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, NHC Key laboratory of Myopia and Related Eye Diseases, Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai Research Center of Ophthalmology and Optometry, Shanghai, China.
Abstract:
Oxidative stress, an imbalance between the body's oxidative and antioxidant systems, contributes markedly to the development of numerous ocular surface diseases, particularly dry eye disease (DED). Effective elimination or reduction of reactive oxygen species (ROS) can halt disease progression and alleviate symptoms. This study presents an innovative thermoresponsive, metal-free carbon nanodot (CD) hydrogel, termed F-CD hydrogel, which exhibits potent neutralization capabilities against multiple free radicals, including OH·, O2-·, and ·DPPH. This hydrogel demonstrates remarkable antioxidant, anti-inflammatory, and antiapoptotic capacity, effectively relieving DED symptoms by eliminating ROS at their source. Furthermore, its thermosensitive characteristics enhance the adherence of CDs to the ocular surface. In mouse models of DED, the F-CD hydrogel accelerates epithelial repair, thickens the corneal epithelium, promotes tear secretion, and boosts goblet cell count by up-regulating protective genes while suppressing those promoting apoptosis and oxidative stress. Coupled with its excellent biocompatibility and reduced administration frequency and treatment duration, the F-CD hydrogel emerges as a promising therapeutic approach for DED.
Insights
This study introduces a novel carbon nanodot hydrogel that effectively combats oxidative stress and inflammation, offering a promising new treatment for dry eye disease (DED) by promoting ocular surface repair and tear production.
Area of Science:
- Biomedical Engineering
- Ophthalmology
- Materials Science
Background:
- Oxidative stress significantly contributes to ocular surface diseases like dry eye disease (DED).
- Reactive oxygen species (ROS) elimination is crucial for halting DED progression and alleviating symptoms.
- Current treatments may have limitations in effectively managing oxidative stress in DED.
Purpose of the Study:
- To develop and evaluate an innovative thermoresponsive, metal-free carbon nanodot (CD) hydrogel (F-CD hydrogel) for DED treatment.
- To assess the antioxidant, anti-inflammatory, and antiapoptotic properties of the F-CD hydrogel.
- To investigate the therapeutic efficacy of the F-CD hydrogel in preclinical DED models.
Main Methods:
- Formulation of a thermoresponsive, metal-free carbon nanodot hydrogel (F-CD hydrogel).
- In vitro assessment of free radical neutralization capabilities (OH·, O2-·, ·DPPH).
- Evaluation of antioxidant, anti-inflammatory, and antiapoptotic effects.
- In vivo testing in mouse models of DED to assess therapeutic outcomes.
Main Results:
- The F-CD hydrogel demonstrated potent neutralization of multiple free radicals.
- It exhibited significant antioxidant, anti-inflammatory, and antiapoptotic capacities.
- In DED mouse models, the hydrogel accelerated epithelial repair, increased corneal thickness, promoted tear secretion, and enhanced goblet cell count.
- The F-CD hydrogel effectively regulated protective and apoptotic genes, reducing oxidative stress.
Conclusions:
- The F-CD hydrogel is a promising metal-free therapeutic agent for dry eye disease.
- Its antioxidant and anti-inflammatory properties, coupled with thermosensitive adherence, offer effective ROS elimination at the source.
- The hydrogel promotes ocular surface healing and improves DED symptoms with good biocompatibility and reduced treatment burden.
