A peptidic network antibody inhibits both angiogenesis and inflammatory response

J Control Release. 2023 Oct:362:715-725. doi: 10.1016/j.jconrel.2023.09.019. Epub 2023 Sep 19.

Abstract

Corneal neovascularization (CNV) is a global threat to human health. Traditional anti-angiogenesis agent may have therapy effect, while the inflammation in disease area remains unsolved. Herein, we reported two binding-induced fibrillogenesis (BIF) peptides as peptidic network antibodies for high-efficient and long-lasting anti-angiogenesis with reduced inflammatory response. BIF peptides could self-assemble into nanoparticles and further perform BIF behavior through binding Ca2+. In vitro, the migration of integrin αvβ3 highly expressed endothelial cells was inhibited by BIF peptides. In vivo, one BIF peptide (0.012 mg/Kg) exhibited higher anti-angiogenesis effect than monoclonal antibody bevacizumab (0.96 mg/Kg) in a CNV rabbit model on day 14, despite that the dose of BIF was only 1.3% of bevacizumab. Meanwhile, the inflammatory response, such as PI3 kinase/Akt pathway in CNV was successfully inhibited as well. The peptidic network antibody could block integrin αvβ3 via a long-term retention mode, which led to long-term therapeutic effect. The study provides BIF peptides as promising therapeutic agents for both anti-angiogenesis and reduced inflammatory response.

Keywords: Anti-angiogenesis; Binding-induced fibrillogenesis; Corneal neovascularization; Inflammation; Peptide.