Personalised deposition maps for micro- and nanoparticles targeting an atherosclerotic plaque: attributions to the receptor-mediated adsorption on the inflamed endothelial cells

摘要

Endothelial inflammation as a prominent precursor to atherosclerosis elicits a distinct pathological surface expression of particular vascular proteins. To exhibit a site-specific behaviour, micro- and nanoparticles, as carriers of therapeutics or imaging agents, can distinguish and use these proteins as targeted docking sites. Here, a computational patient-specific model capturing the exclusive luminal qualities has been developed to study the transport and adsorption of particles decorated with proper antibodies over an atherosclerotic plaque located in the LAD artery of the patient. Particles, in nano- and micron sizes, have been decorated with Sialyl Lewis(x) (sLe(x)), P-selectin aptamer (PSA), and ICAM-1 antibody (abICAM) to target the three of the most well-known endothelial adhesion proteins that display pathological expressions on the plaque surface, namely E-selectin, ICAM-1, and P-selectin. We learned that in the receptor-mediated adhesive dynamics in pathological contexts, parameters such as specific diffusivity of ligand-receptor pairs and the affinity constant play crucial roles in the final amount and homogeneity of surface density of adsorbed particles (SDA). In spite of ascending nature of SDAs with the increase in particle size, our model specified that the alteration in results due to increase in particle diameter can be insignificant depending upon the special parameters associated with the type of ligand-receptor bonds. Also, the combination of 95.1% sLe(x) and 4.9% PSA ligands for dual-targeting 800-nm particles was introduced as the optimal decorating arrangement for which the surface of plaque experiences a significant SDA along with a homogeneously improved deposition pattern. Finally, the key results of this work were compared with the results of similar experiments in a pulsatile flow chamber and a relevant in vivo test.