Supramolecular Self-Assembled Multivalent Anti-VEGF Protein Nanospheres for Prolonged Ocular Retention.

Area of Science:

• Biochemistry
• Ophthalmology
• Nanotechnology

Background:

• Retinal vascular diseases require long-acting anti-vascular endothelial growth factor (VEGF) agents.
• Current treatments face challenges in achieving prolonged half-life, high bioactivity, and suitable viscosity.

Purpose of the Study:

• To develop and evaluate a supramolecular anti-VEGF protein nanosphere (Fer-VD) with enhanced pharmacokinetic properties for treating retinal vascular diseases.
• To assess Fer-VD's stability, bioactivity, and ocular retention compared to existing therapies.

Main Methods:

• Engineered Fer-VD by fusing VEGF receptor (VEGFR) binding domain to ferritin, forming a 24-mer nanostructure.
• Evaluated VEGF binding affinity, inhibition of VEGF-induced signaling in vitro and cellular assays.
• Assessed biophysical properties (stability, viscosity) and performed intravitreal pharmacokinetic studies in rabbits.

Main Results:

• Fer-VD self-assembled into a stable nanostructure with high-affinity VEGF binding and potent anti-VEGF activity.
• Demonstrated excellent thermal and colloidal stability, favorable viscosity, and solution homogeneity at high concentrations.
• Achieved a two-fold longer vitreous half-life than aflibercept in rabbit models, with localized retinal surface retention.

Conclusions:

• Fer-VD is a promising long-acting VEGF antagonist for retinal vascular diseases.
• Its supramolecular design confers enhanced ocular retention and favorable pharmacokinetic properties.
• Fer-VD represents a potential advancement in the therapeutic landscape for retinal vascular diseases.