Generalized blood vessel models for magnetic nanoparticle-based oncology: geometric and microfluidic properties

Superparamagnetic iron oxide nanoparticles (SPIONs) represent an emerging class of nanoparticles that face increasing applications in medicine, in particular in nanoparticle-based oncology. Their superparamagnetic properties allow for the magnetic steering and the interlinked targeted and localized delivery of pharmaceuticals. The development of nanoparticle-based therapies requires a deep understanding of geometry-hydrodynamics-adhesion interactions, motivating the generation of blood vessel models. The present work addresses the geometry-dependent propagation of SPIONs under magnetic steering through generalized, transferable geometries. Such geometries were derived based on generalized, statistical considerations of branch-dependent vessel diameters, yielding a reproducible and transferable testing environment independent of individual angiographic data. Based on stereolithographic additive manufacturing, fluidic models with varied blood vessel diameters and branching orders were manufactured and tested under varying magnetic steering conditions, injected SPION concentration, and flow rate. Through optical in situ measurements and complementary ex situ scanning electron microscopy, a significant influence of flow-regime-dependent hydrodynamic effects on magnetic steerability could be identified. Experimental findings suggest that while reduced flow rates were associated with locally laminar flows that promoted sedimentation and enabled limited magnetic redistribution of SPION-containing colloidal solutions at a magnetic flux density of B = 0.35 T, increased flow rates and interlinked unsteady flows were shown to impair the magnetically controlled, local SPION deposition. Hence, flow conditions present in larger arteries and bifurcations during SPION injection can be shown to significantly influence the quantitative magnetic steering of SPIONs in vascular-inspired fluidic channel structures, displaying enhanced local particle residence times and redistribution of SPIONs under low-flow conditions.