Size-Dependent <i>In Vivo</i> Transport of Nanoparticles: Implications for Delivery, Targeting, and Clearance.

Abstract

Understanding the <i>in vivo</i> transport of nanoparticles provides guidelines for designing nanomedicines with higher efficacy and fewer side effects. Among many factors, the size of nanoparticles plays a key role in controlling their <i>in vivo</i> transport behaviors due to the existence of various physiological size thresholds within the body and size-dependent nano-bio interactions. Encouraged by the evolving discoveries of nanoparticle-size-dependent biological effects, we believe that it is necessary to systematically summarize the size-scaling laws of nanoparticle transport <i>in vivo</i>. In this review, we summarized the size effect of nanoparticles on their <i>in vivo</i> transport along their journey in the body: begin with the administration of nanoparticles via different delivery routes, followed by the targeting of nanoparticles to intended tissues including tumors and other organs, and eventually clearance of nanoparticles through the liver or kidneys. We outlined the tools for investigating the <i>in vivo</i> transport of nanoparticles as well. Finally, we discussed how we may leverage the size-dependent transport to tackle some of the key challenges in nanomedicine translation and also raised important size-related questions that remain to be answered in the future.