Norbornene-chitosan nanoparticles with and without a conjugated VEGF-peptide analog to promote vascularization

Abstract

Impaired angiogenesis in skin chronic wounds prolongs inflammation and compromises wound healing. Several strategies have been attempted to improve vascularization, such as application of growth factors, like the vascular endothelial growth factor (VEGF). However, VEGF is expensive, has a short half-life in vivo and has been associated to tumorigenesis when used in high concentrations. QK peptide is a shorter (15 amino acids), synthetic, VEGF-mimetic peptide with improved stability and lower production cost. However, the residence time and half-life of QK may be further improved by conjugation to nanoparticles (NP). Herein, QK was conjugated onto norbornene-chitosan (NorChit) NP in a “one-pot" microfluidics device using thiol-norbornene “photoclick” chemistry. An in vitro proliferation assay using human umbilical vein endothelial cells (HUVEC) showed the higher efficacy of QK-NorChit NP (Ø = 111 ± 74 nm) in inducing HUVEC metabolic activity compared to soluble Cys-QK, highlighting the advantage of conjugation. However, when tested in vivo (chick chorioallantoic membrane assay; CAM), all the NP were pro-angiogenic, regardless of being decorated with QK or not. Interestingly, bare NorChit NP were superior to both VEGF and QK-NorChit NP in stimulating angiogenesis. Therefore, NorChit NP with and without QK may be useful to promote vascularization in chronic wounds.