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Published on: June 16, 2018
Fluorinated ROS-responsive polycation enables noninvasive siRNA Delivery for the treatment of corneal
Yifei Chen1, Xin Wang1, Yong Duan1
1National Engineering Research Center of Ophthalmology and Optometry, School of Biomedical Engineering, School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China.
Abstract:
Corneal neovascularization (CNV) is a vision-threatening condition characterized by abnormal blood vessel growth into the avascular cornea, impairing its transparency and visual function. CNV is driven by an imbalance between pro- and anti-angiogenic factors, notably the overexpression of vascular endothelial growth factor (VEGF), exacerbated by inflammation and oxidative stress. Current treatments, including anti-VEGF and anti-inflammatory agents, are limited by poor bioavailability and invasive administration. In this study, we developed a fluorinated polycation for non-invasive delivery of siVEGFA along with ROS scavenging functionality to combat CNV. This multifunctional polymer exhibits enhanced ocular surface penetration via fluorination effect, efficient siRNA binding and delivery, and ROS-scavenging capacity. It demonstrated high biocompatibility, suppressed VEGFA expression, and significantly inhibited CNV progression in a mouse alkali burn model. These results highlight the promise of fluorinated, stimuli-responsive polymers as a dual-functional platform for safe, effective, and non-invasive treatment of ocular neovascular disorders. STATEMENT OF SIGNIFICANCE: CNV is a major cause of vision loss, yet current treatments rely on invasive injections or anti-inflammatory drugs, which can hinder corneal healing and reduce patient compliance. This study presents a fluorinated, ROS-responsive polycation that enables non-invasive, topical siRNA delivery while simultaneously combatting oxidative stress. Unlike conventional carriers, fluorination improves ocular penetration and intracellular delivery. By combining VEGFA knockdown with intrinsic antioxidant activity, this platform effectively suppresses neovascularization without delaying epithelial repair. This study advances the field of ocular gene therapy by offering a safer, injection-free alternative. It also highlights the potential of multifunctional polymer systems for treating chronic ocular vascular diseases.
Insights
A new fluorinated polymer delivers gene therapy non-invasively to treat corneal neovascularization (CNV) by reducing vascular endothelial growth factor (VEGF) and oxidative stress, offering a safer alternative to eye injections.
Area of Science:
- Ophthalmology
- Biomaterials Science
- Gene Therapy
Background:
- Corneal neovascularization (CNV) threatens vision due to abnormal blood vessel growth, driven by factors like vascular endothelial growth factor (VEGF) and oxidative stress.
- Current treatments for CNV often involve invasive injections and may impede corneal healing, limiting patient compliance and efficacy.
Purpose of the Study:
- To develop a novel fluorinated polycation for non-invasive, topical delivery of small interfering RNA targeting VEGF (siVEGFA) and reactive oxygen species (ROS) scavenging.
- To evaluate the efficacy and safety of this dual-functional polymer in combating CNV in a preclinical model.
Main Methods:
- Synthesis and characterization of a fluorinated polycation with ROS-scavenging capabilities.
- In vitro assessment of polymer biocompatibility, siRNA binding, and delivery efficiency.
- In vivo evaluation of the polymer's effect on CNV progression in a mouse alkali burn model, assessing VEGFA expression and neovascularization.
Main Results:
- The fluorinated polycation demonstrated enhanced ocular surface penetration and efficient delivery of siVEGFA.
- The polymer effectively suppressed VEGFA expression and significantly inhibited CNV progression in the mouse model.
- The treatment showed high biocompatibility and did not delay corneal epithelial repair.
Conclusions:
- Fluorinated, ROS-responsive polycations offer a promising platform for safe, effective, and non-invasive treatment of ocular neovascular disorders.
- This dual-functional approach combines gene silencing with antioxidant activity for superior therapeutic outcomes in CNV.
- The developed polymer represents a significant advancement in ocular gene therapy, providing an injection-free alternative for vision-threatening conditions.
