Sodium hyaluronate/lysine nanoparticles loaded with si-VEGF-A inhibits corneal neovascularization.

OBJECTIVE

This study designed sodium hyaluronate/lysine (SH/Lys)-based nanoparticles loaded with vascular endothelial growth factor A (VEGF-A) siRNA (V-SH/Lys), aiming to effectively treat corneal neovascularization (CNV) by specifically inhibiting the expression of VEGF-A.

METHODS

The particle size, zeta potential and stability of the V-SH/Lys nanoparticles loaded with si-VEGF-A were tested. The effects of V-SH/Lys nanoparticles on the tube formation and migration of vascular endothelial cells were evaluated through Transwell, cell scratch assay and cell tube formation assay. A rat model of CNV was established, and the extent of the neovascularization was quantified. The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in the cornea were also measured. The safety of V-SH/Lys nanoparticles was evaluated through cytotoxicity tests on corneal epithelial cells and pathological examinations of rat fundus tissues.

RESULTS

The V-SH/Lys nanoparticles exhibited a particle size of 204.5 ± 38.3 nm, a zeta potential of +17.90 ± 6.46 mV, and demonstrated good stability as shown by high performance liquid chromatography (HPLC). In vitro experiments demonstrated that V-SH/Lys could block formation of the tubular structures and migration of vascular endothelial cells. In the CNV model induced by corneal alkali burn in rats, the area of new blood vessels in the V-SH/Lys group was smaller than that in the control group (P<0.01), and the levels of corneal inflammatory factors (TNF-α, IL-6) were significantly reduced. Moreover, V-SH/Lys nanogel exhibited no obvious toxicity to corneal epithelial cells, and no abnormalities were observed in the rat fundus tissues, indicating its favorable safety profile.

CONCLUSION

This study has confirmed that V-SH/Lys nanoparticles, by targeting and regulating VEGF-A, provide an efficient, safe and non-invasive treatment strategy for CNV, and have potential for clinical application.