Suppression of pathological neovascularization by anti-Flt1 peptide functionalized DNA tetrahedron

Angiogenesis is an important and necessary process in tissue regeneration and recovery, but suppressing such process is also a critical therapeutic consideration in some diseases including tumor and corneal neovascularization. Currently, pathological angiogenesis is mainly inhibited through the blockade of the interaction between vascular endothelial growth factor receptor (VEGFR) and its ligands. Compared to traditional anti-angiogenic agents such as monoclonal antibody and tyrosine kinase inhibitor, polypeptide has gained growing interests for high unit activity, few adverse reactions, and low costs. Among them, anti-Flt1 (AF) peptide could inhibit VEGFR1-induced endothelial cell migration and tube formation, showing excellent anti-angiogenic activity. Addressing the issues of low water solubility, instability, and poor bioavailability would significantly hinder the applications of AF. Herein, we prepared an AF functionalized tetrahedral framework nucleic acid (tFNA@AF) to overcome the abovementioned limitations of AF. The tFNA@AF presented enhanced structural stability and cellular uptake of AF, and exhibited superior bioavailability and satisfying anti-angiogenic effectiveness in vitro. Furthermore, tFNA@AF also demonstrated high-efficiency pathological angiogenesis inhibition on tumor-bearing mice of triple-negative breast cancer and corneal neovascularization of cornea cauterized rats, two typical models of tumor and traumatic cornea where angiogenesis is not anticipant. Our tFNA@AF as a novel polypeptide-nucleic acid conjugated nanomaterials showed superior bioavailability and high anti-angiogenic effectiveness, suggesting that with incremental improvements the nanomedicine may offer potentially useful treatment aid for anti-angiogenic therapy to prevent tumor growth and corneal neovascularization.