Modelling the Transport of Nanoparticles under Blood Flow using an Agent-based Approach

Abstract

Blood-mediated nanoparticle delivery is a new and growing field in the development of therapeutics and diagnostics. Nanoparticle properties such as size, shape and surface chemistry can be controlled to improve their performance in biological systems. This enables modulation of immune system interactions, blood clearance profile and interaction with target cells, thereby aiding effective delivery of cargo within cells or tissues. Their ability to target and enter tissues from the blood is highly dependent on their behaviour under blood flow. Here we have produced an agent-based model of nanoparticle behaviour under blood flow in capillaries. We demonstrate that red blood cells are highly important for effective nanoparticle distribution within capillaries. Furthermore, we use this model to demonstrate how nanoparticle size can selectively target tumour tissue over normal tissue. We demonstrate that the polydispersity of nanoparticle populations is an important consideration in achieving optimal specificity and to avoid off-target effects. In future this model could be used for informing new nanoparticle design and to predict general and specific uptake properties under blood flow.

Targeted drug delivery of near IR fluorescent doxorubicin-conjugated poly(ethylene glycol) bisphosphonate nanoparticles for diagnosis and therapy of primary and metastatic bone cancer in a mouse model

“…The uptake of the Cy 7-conjugated BP NPs within the tumor and their retention over time can be explained by the high affinity of the BP functional group to Ca 2+ ions, thereby endowing these BP NPs with the ability to preferentially target human osteosarcoma Saos-2 tumor. The initial uptake of the control NPs could be explained by the EPR effect, where increased vascular permeability leads to leakage of the blood-borne NPs into the tumor [42–45]. The specific uptake of BP NPs in osteosarcoma tumor was confirmed on repetition of the experiment, using a tumor xenograft formed from SW620 human colon epithelial adenocarcinoma cell line, where no preferential uptake was evident.…”

Cellular Shuttles: Monocytes/Macrophages Exhibit Transendothelial Transport of Nanoparticles under Physiological Flow

“…For example, agent-based modeling studies of NP capillary transport in complete blood have emphasized the significant effect that red blood cells play on NP hemodynamics. 47 In all such experimental designs, the flow studies were conducted with unidirectional, noncirculating flow. As such, it may be more prudent to look for a physical explanation to describe why increasing shear stress results in increased particle uptake, rather than attributing these phenomena to biological effects or NP properties.…”

Design of Nanoparticle-Based Carriers for Targeted Drug Delivery

“…In the microvascularture, a convection-diffusion-reaction model was developed for nanoparticle concentration studies. G. Fullstone 80 used flexible large-scale agent based modeling (FLAM) coupled with computational fluid dynamics (CFD) to study NP distribution in capillaries. In the microvasculature, red blood cells aid NP dispersion to the vessel walls and modify the EPR effect.…”

“…In the microvasculature, red blood cells aid NP dispersion to the vessel walls and modify the EPR effect. It was reported that larger NPs (submicron size) are more likely to be pushed to the vessel walls than smaller NPs, which in turn gives them a greater chance of permeating through diseased vasculatures to reach the target cells 80 . NP adhesion with endothelial cells modeled with IMEFEM suggests that NP shape affect adhesion, with spherical NPs having a lower lateral drift velocity compared with ellipsoids.…”