2024 AIChE Annual Meeting
Patchy, Locally Multivalent VEGF-Functionalization of Heterogeneous Liposomes May Safely and Effectively Activate Angiogenesis in Vitro
Among the leading causes of death, ischemic heart disease results in heart attacks and failure due to insufficient oxygen supply as a result of reduced blood circulation. Current revascularization therapies that stimulate angiogenesis via vascular endothelial growth factors (VEGF) provide only short-term effects due to the short blood clearance half-lives of these agents. While various nanostructures such as hydrogels and peptide amphiphile nanofibers have been applied to prolong the circulation time of proteins, safety concerns limit their potential clinical applications. In addition, to ensure activation of the VEGF receptor, long association times with the VEGF ligand are needed. To address both challenges, we engineered liposomes with stably phase-separated lipid domains, which were functionalized with high local surface concentrations of the VEGF-targeting peptides. This locally multivalent surface architecture, we have previously demonstrated, results in long association times of the functionalized liposomes with a single receptor via continuous exchange of different ligands (from the same liposome) with the same receptor. Additionally, liposomes are an alternative well-studied drug delivery method that have a noticeably lower immunogenic response and longer clearance times. This study uses VEGF-peptides conjugated to lipids which preferentially partition in the stably phase-separated lipid domains of 100nm-in-diameter liposomes. This lipid vesicle topography forms a “sticky patch” on the liposomes that is aimed to effectively activate VEGFR and stimulate angiogenesis that is safe. To evaluate the angiogenic stimulation of these VEGF-functionalized-liposomes, human umbilical vein endothelial cells (HUVECs) were used as an in vitro 2D model. Future evaluation of the liposome safety and angiogenic stimulation may be conducted in 3D in vitro models such as spheroids containing HUVEC.