The preferential targeting of the diseased microvasculature by disk-like particles

Different classes of nanoparticles (NPs) have been developed for controlling and improving the systemic administration of therapeutic and contrast agents. Particle shape has been shown to be crucial in the vascular transport and adhesion of NPs. Here, we use mesoporous silicon non-spherical particles, of disk and rod shapes, ranging in size from 200 nm to 1800 nm. The fabrication process of the mesoporous particles is described in detail, and their transport and adhesion properties under flow are studied using a parallel plate flow chamber. Numerical simulations predict the hydrodynamic forces on the particles and help in interpreting their distinctive behaviors. Under microvascular flow conditions, for disk-like shape, 1000 x 400 nm particles show maximum adhesion, whereas smaller (600 x 200 nm) and larger (1800 x 600 nm) particles adhere less by a factor of about two. Larger rods (1800 x 400 nm) are observed to adhere at least 3 times more than smaller ones (1500 x 200 nm). For particles of equal volumes, disks adhere about 2 times more than rods. Maximum adhesion for intermediate sized disks reflects the balance between adhesive interfacial interactions and hydrodynamic dislodging forces. In view of the growing evidence on vascular molecular heterogeneity, the present data suggests that thin disk-like particles could more effectively target the diseased microvasculature as compared to spheres and slender rods. (C) 2012 Elsevier Ltd. All rights reserved.