Nanoparticle transport and binding dynamics in blood flow

Nanoparticulate systems have been widely used in diagnostic imaging and targeted therapeutic applications in recent years. Most current studies on nanoparticle drug delivery considered a Newtonian fluid with suspending spherical nanoparticles. However, blood is a complex biological fluid composed of deformable cells, proteins, platelets, and plasma. For blood flow in capillary, arterioles and venules, the particulate nature of the blood need to be considered in the delivery process. Non-Newtonian effects such as the cell-free-layer and nanoparticle-cell interaction will largely influence both the dispersion and binding rates, thus impact targeted delivery efficacy. A 3D multiscale particle-cell hybrid model is developed to model nanoparticle transport, dispersion, and adhesion dynamics in blood suspension. The motion and deformation of red blood cell is captured through Immersed Finite Element method. The motions and bindings of individual nanoparticles of various shapes are tracked through Brownian adhesion dynamics and molecular ligand-receptor binding kinetics. Nanoparticle dispersion and binding coefficients are derived from the developed model under various rheology conditions. The influences of vascular flow rate, geometry, nanoparticle size on nanoparticle distribution and delivery efficacy are characterized. A non-uniform nanoparticle distribution profile with higher particle concentration near the vessel wall is observed. Such distribution leads to 50{\%} higher particle binding rate compared to the case without RBC considered. The tumbling motion of RBCs in the core region of the capillary is found to enhance nanoparticle dispersion. The modeled binding results are validated through designed experiments in microfluidic devices.