Dual Affinity Nanoparticles for the Transport of Therapeutics from Carrier Cells to Target Cells under Physiological Flow Conditions

In this study, a novel two-stage nanoparticle delivery
platform
was developed based on the dual functionalization of a liposome with
moieties that have fundamentally different strengths of adhesion and
binding kinetics. The essential concept of this system is that the
nanoparticles are designed to loosely bind to the carrier cell until
they come into contact with the target cell, to which they bind with
greater strength. This allows the nanoparticle to be transferred from
one cell to another, circulating for longer periods of time in the
blood and delivering the therapeutic agent to the target circulating
tumor cell. Liposomes were prepared using the lipid cake and extrusion
technique, then functionalized with E-selectin (ES), anti-cell surface
vimentin antibody fragments, and TRAIL via click chemistry. The binding
of dual affinity (DA) liposomes was confirmed with the neutrophil-like
cell line PLB985, the colorectal cancer cell line HCT116, and healthy
granulocytes isolated from peripheral whole blood under physiologically
relevant fluid shear stress (FSS) in a cone-and-plate viscometer.
Transfer of the DA liposomes from PLB985 to HCT116 cells under FSS
was greater compared to all of the control liposome formulations.
Additionally, DA liposomes demonstrated enhanced apoptotic effects
on HCT116 cells in whole blood under FSS, surpassing the efficacy
of the ES/TRAIL liposomes previously developed by the King Lab.