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Self-Cascade API Nanozyme for Synergistic Anti-Inflammatory, Antioxidant, and Ferroptosis Modulation in the Treatment
Hongwei Wang1,2, Yang Yang1,3,4, Huimin Yu1,4
1State Key Laboratory Cultivation Base Shandong Key Laboratory of Eye Diseases, Eye Institute of Shandong First Medical University, Qingdao, 266071, China.
Abstract:
Corneal neovascularization is a common pathological ocular change that can severely impairs vision, potentially leading to blindness. Although steroids and non-steroidal anti-inflammatory drugs are the primary treatments, their side effects, such as ocular hypertension, eye irritation, and corneal lysis, limit their widespread use. In the present study, an active pharmaceutical ingredient (API) nanozyme (PC-DS NE) is developed through the metal-organic coordination of ferrous sulfate with the anti-inflammatory agent diclofenac sodium and the natural antioxidant proanthocyanidin. PC-DS NE exhibited a spheroid morphology with a particle size of 39.7 ± 5.2 nm, and could achieve the short-term release of diclofenac sodium and sustained release of proanthocyanidin. Notably, the PC-DS NE possessed favorable biocompatibility, self-cascade redox regulation capacity, and significant anti-inflammatory activity. In corneal alkali burn experiments, PC-DS NE effectively inhibited corneal neovascularization by scavenging reactive oxygen species, inhibiting the expression of inflammatory cytokines and pro-angiogenic factors, and down-regulating ferroptosis. These synergistic effects highlighted the potential of PC-DS NE as a promising treatment for ocular inflammatory diseases.
Insights
A novel nanozyme (PC-DS NE) effectively treats corneal neovascularization by reducing inflammation and oxidative stress. This new treatment offers a promising alternative for ocular inflammatory diseases.
Area of Science:
- Ophthalmology
- Materials Science
- Nanotechnology
Background:
- Corneal neovascularization impairs vision and can lead to blindness.
- Current treatments like steroids have significant side effects, limiting their use.
- There is a need for safer and more effective treatments for ocular inflammatory diseases.
Purpose of the Study:
- To develop and evaluate a novel nanozyme (PC-DS NE) for treating corneal neovascularization.
- To investigate the anti-inflammatory and anti-angiogenic properties of PC-DS NE.
- To assess the potential of PC-DS NE as a therapeutic agent for ocular inflammatory diseases.
Main Methods:
- Synthesized PC-DS NE via metal-organic coordination of ferrous sulfate, diclofenac sodium, and proanthocyanidin.
- Characterized PC-DS NE morphology and particle size (39.7 ± 5.2 nm).
- Evaluated short-term and sustained release profiles of diclofenac sodium and proanthocyanidin, respectively.
- Assessed biocompatibility, redox regulation, and anti-inflammatory activity in vitro.
- Tested efficacy in corneal alkali burn models, analyzing reactive oxygen species scavenging, inflammatory cytokine expression, pro-angiogenic factors, and ferroptosis.
Main Results:
- PC-DS NE demonstrated spheroid morphology and optimal particle size for nanomedicine.
- The nanozyme exhibited favorable biocompatibility and potent anti-inflammatory effects.
- PC-DS NE effectively inhibited corneal neovascularization in vivo.
- Mechanism of action involves scavenging reactive oxygen species, reducing inflammatory markers, and down-regulating ferroptosis.
Conclusions:
- PC-DS NE is a promising nanozyme with significant therapeutic potential for corneal neovascularization.
- Its multi-modal mechanism of action, including anti-inflammatory and anti-angiogenic effects, addresses key pathological pathways.
- PC-DS NE represents a viable alternative to conventional treatments for ocular inflammatory conditions.
