Multiscale modeling of protein membrane interactions for nanoparticle targeting in drug delivery

Nanoparticle (NP)-based imaging and drug delivery systems for systemic (e.g. intravenous) therapeutic and diagnostic applications are inherently a complex integration of biology and engineering. A broad range of length and time scales are essential to hydrodynamic and microscopic molecular interactions mediating NP (drug nanocarriers, imaging agents) motion in blood flow, cell binding/uptake, and tissue accumulation. A computational model of time-dependent tissue delivery, providing in silico prediction of organ-specific accumulation of NPs, can be leveraged in NP design and clinical applications. In this article, we provide the current state-of-the-art and future outlook for the development of predictive models for NP transport, targeting, and distribution through the integration of new computational schemes rooted in statistical mechanics and transport. The resulting multiscale model will comprehensively incorporate: (i) hydrodynamic interactions in the vascular scales relevant to NP margination; (ii) physical and mechanical forces defining cellular and tissue architecture and epitope accessibility mediating NP adhesion; and (iii) subcellular and paracellular interactions including molecular-level targeting impacting NP uptake.