Recombinant IFN-α2a-NGR Exhibits Higher Inhibitory Function on Tumor Neovessels Formation Compared with IFN-α2a in Vivo and in Vitro
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We previously reported that NGR-fused IFN-α2a (IFN-α2a-NGR) exhibited similar biological activities with native IFN-α2a and was well-tolerated in mice, rats and monkeys. In the current study, we evaluated the mechanisms of this fusion protein on angiogenesis and tumor formation. Our data indicated that IFN-α2a-NGR has the ability to target tumor blood vessels while preserving the original function of native IFN-α2a. IFN-α2a-NGR was found to be concentrated in the tumor tissues, particularly around the vessel areas. In contrast to IFN-α2a, IFN-α2a-NGR significantly decreased microvessel density and increased the apoptosis of vascular endothelial cells. IFN-α2a-NGR also decreased the expression of VEGF and bFGF in tumor cells. Significant inhibition of invasion, migration, tube formation and induction of apoptosis of endothelial cells were observed in IFN-α2a-NGR-treated group. In conclusion, results from in vitro and in vivo experiments indicate that IFN-α2a-NGR is a promising anti-angiogenic agent with greater therapeutic efficacy than IFN-α2a.
Research advances in peptide‒drug conjugates.
Gong L, Zhao H, Liu Y, Wu H, Liu C, Chang S Acta Pharm Sin B. 2023; 13(9):3659-3677.
PMID: 37719380 PMC: 10501876. DOI: 10.1016/j.apsb.2023.02.013.