Fucoidan/bis-MPA-based dendrimer nanoparticles with intrinsic anti-angiogenic activity for oncology applications

Abstract

Nanoparticles with intrinsic anti-angiogenic activity hold strong promise in cancer nanomedicine, as they can both help suppress metastasis and deliver therapeutics, offering a dual strategy for addressing the disease. In this study, fucoidans from F. vesiculosus and U. pinnatifida with two different molecular weights (M_W) of each were initially screened for in vitro anti-angiogenic potential using the tube formation assay with HUVEC cells. The higher M_W fucoidans, which represent native M_W fucoidan, exhibited greater anti-angiogenic activity and were subsequently combined with 2,2-bis(hydroxymethyl)propionic acid (bis-MPA)-based dendrimers (generation 2) at different fucoidan/dendrimer (F/D) mass ratios to form self-assembled nanoparticles through electrostatic interactions. Optimisation yielded two nanoparticle types with positive (F/D = 1 : 2) and negative (F/D = 2 : 1) zeta potentials, which were characterised for their physicochemical properties, including hydrodynamic diameter, zeta potential, chemical composition (FTIR), and morphology (TEM). These nanoparticles presented a near-spherical shape, were cytocompatible, and did not cause haemolysis. Positively charged nanoparticles showed stronger anti-angiogenic activity than negatively charged ones. Since the dendrimers alone were also anti-angiogenic, the overall effect likely results from the combined contribution of both components, with nanoparticle assembly potentially playing a role. Overall, these findings highlight the potential of fucoidan/dendrimer nanoparticles as multifunctional platforms for cancer nanomedicine, by targeting angiogenesis and potentially serving as drug or gene delivery systems.