Enhancing Bioactivity, Physicochemical, and Pharmacokinetic Properties of a Nano-Sized, Anti-Vegfr2 Adnectin, Through Pasylation Technology Publisher Pubmed



Aghaabdollahian S¹ ; Ahangari Cohan R¹ ; Norouzian D¹ ; Davami F² ; Asadi Karam MR³ ; Torkashvand F⁴ ; Vaseghi G⁵ ; Moazzami R² ; Latif Dizaji S¹
Source: Scientific Reports Published:2019

Abstract

The crucial role of VEGF receptor 2 (VEGFR2) signaling in the angiogenesis and metastasis of solid tumors has prompted the development of inhibitors with minimal bystander effects. Recently, Adnectin C has attracted attention for cancer treatment. To overcome the problematic properties of Adnectin, a novel form of Adnectin C has been designed by its fusion to a biodegradable polymeric peptide containing Pro/Ala/Ser (PAS) repetitive residues. E. coli-expressed recombinant fused and unfused proteins were compared in terms of bioactivity, physicochemical, and pharmacokinetic properties using standard methods. Dynamic light scattering (DLS) analysis of PASylated adnectin C revealed an approximate 2-fold increase in particle size with a slight change in the net charge. Additionally, fusion of the PAS sequence improved its stability against the growth of thermo-induced aggregated forms. The high receptor-binding and improved binding kinetic parameters of PASylated Adnectin C was confirmed by ELISA and surface plasmon resonance assays, respectively. Pharmacokinetic studies showed a noticeable increase in the terminal half-life of Adnectin C-PAS#1(200) by a factor of 4.57 after single dose by intravenous injection into female BALB/c mice. The results suggest that PASylation could offer a superior delivery strategy for developing Adnectin-derived drugs with improved patient compliance. © 2019, The Author(s).