"Hook&Loop" multivalent interactions based on disk-shaped nanoparticles strengthen active targeting

Abstract

How to enhance active targeting efficiency remains a challenge. Multivalent interactions play a crucial role in improving the binding ability between ligands and receptors. It is hypothesized that nanoparticles bearing a flat conformation attain simultaneous formation of multiple ligand-receptor bindings, which could be vividly metaphorized by the "Hook&Loop" rationale. In this study, spherical, rod-shaped and disk-shaped folic acid-modified red blood cell membrane-coated biomimetic mesoporous silica nanoparticles (FRMSNs) were prepared to verify the shape-based multivalent interactions. The fundamental concepts of multivalent interactions have been proved by a series of both in vitro and in vivo evaluations. Physical characterization confirmed the morphology, shape and surface features of FRMSNs. Strengthened binding and internalization of disk-shaped FRMSNs by K562 cells stresses the merits of multivalent interactions. Whereas Bio-TEM visually demonstrates the proposed "plane" contact of disk-shaped particles with cells, quantification further confirmed strengthened "plane" binding affinity with folate binding proteins owing to multivalent interactions. In K562 xenograft mice, doxorubicin-loaded disk-shaped FRMSNs effectively slowed down chronic myeloid leukemia progression. It is concluded that disks favor multivalent interactions which leads to enhanced active targeting efficiency.

Keywords: Chronic myeloid leukemia; Doxorubicin; Drug delivery; Multivalent interaction; Nanoparticle; Shape; Targeting.