Multifunctional Biomimetic Nanotherapeutics for Anti-Oxidative and Anti-Inflammatory Synergistic Therapy of Corneal Neovascularization

Abstract

Corneal neovascularization (CNV) is a debilitating ocular surface disease that severely compromises visual function and carries a significant risk of vision loss. Despite its clinical impact, the development of effective and safe pharmacological treatments for CNV remains an unmet medical need. The pathogenesis of CNV is largely driven by inflammation and excessive oxidative stress. In this study, we introduce a novel nanotherapeutic strategy utilizing vanadium carbide quantum dots (V₂C QDs) with intrinsic nanozyme properties, co-encapsulated with a plasmid encoding interleukin-10 (IL-10) within a biomimetic metal-organic framework (MOF) for the treatment of CNV. To enhance targeting and biocompatibility, the nanoparticles (NPs) are further coated with mesenchymal stem cell (MSC)-derived cell membrane vesicles (CMVs), yielding the final nanomedicine designated as MOF-V₂C-Plasmid@CMVs (MVPC). In vitro studies demonstrate that MVPC NPs effectively scavenge reactive oxygen species (ROS) induced by tert-butyl hydroperoxide (tBOOH), mitigating oxidative stress. Moreover, the successful delivery and expression of the IL-10 plasmid in RAW264.7 cells result in elevated IL-10 secretion, showcasing robust anti-inflammatory activity. The CMV coating facilitates targeted delivery, enabling the efficient accumulation of MVPC NPs in the CNV region following topical administration via eye drops. In vivo experiments in CNV model rats reveal that MVPC nanotherapeutics significantly suppress neovascularization without inducing adverse effects. Collectively, this study provides proof of concept for a multifunctional nanotherapeutic platform targeting CNV, offering a promising and clinically translatable approach for the treatment of this challenging ocular disease.