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Copper Sulfide Nanoparticles Protect Against Fundus Neovascularization Diseases and Inhibit NF-κB Signaling Pathway
Yuxin Jiang1,2,3,4, Guanran Zhang1,2,3,4, Lin Zhang5
1Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Purpose:
This study aims to investigate whether copper sulfide nanoparticles (CuS NPs) protect against fundus neovascularization diseases (FNDs) and to explore the underlying mechanism of the anti-angiogenesis.
Materials And Methods:
The characterization and biocompatibility of CuS NPs were assessed in human umbilical vein endothelial cells (HUVECs) and in retinas and major organs. Anti-angiogenic effects were evaluated in vitro using HUVECs through migration, sprouting, and proliferation assays. In vivo efficacy was tested in neonatal retinal vascular development, oxygen-induced retinopathy and laser-induced choroidal neovascularization mouse model. Transcriptomic analysis of CuS NPs-treated HUVECs was performed, followed by validation of key signaling pathways using real-time PCR and western blotting.
Results:
Synthesized CuS NPs exhibited defined characteristics and demonstrated good biocompatibility at tested concentrations. They significantly inhibited HUVECs migration, sprouting, and proliferation. In vivo, CuS NPs attenuated retinal neovascularization and suppressed and choroidal neovascularization. Transcriptomic profiling and further validation revealed a significant downregulation of the nuclear factor-kappa B signaling pathway and its downstream cascades, coinciding with the observed anti-angiogenic outcomes upon CuS NPs treatment.
Conclusions:
CuS NPs may act as a promising therapeutic candidate for FNDs treatment.
