Multiscale Imaging of Nanoparticle Drug Delivery

Nanoparticles have recently had a major impact on basic biosciences, the pharmaceutical industry, and preclinical and translational medicine by enabling targeted delivery of therapeutic cargo to cells and tissues. The capacity to specifically tailor the pharmacokinetics, biodistribution, and longterm fate of therapeutic molecules for specific diseases and to avoid off-target side effects is a tremendously promising capability of these materials. However targeting of nanoparticle therapies from systemic circulation is very inefficient, and our understanding of the fundamental processes dictating in vivo fate remains limited, making it challenging to determine how to optimally and rationally design these materials for maximum efficacy. Recently multi-modal, multi-scale imaging technologies have emerged that have helped to improve our insight into these processes. Theranostic imaging agents have provided real-time and quantitative readouts of drug distribution and therapeutic response, multimodal imaging platforms have allowed a multi-scale analysis of distribution from the levels of cells to tissues, and exciting applications in live-animal tissue microscopy have provided key insights at the cellular level. In this review, we describe how multiscale imaging has shaped our ability to optimize nanoparticle drugs and discuss future directions that are expected to further catalyze clinical translation.