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.
Keywords: Enhanced permeability and retention, fluorescence, intravital microscopy, magnetic resonance imaging, nanomaterials,
nanomedicine, nanotechnology, positron emission tomography, quantum dots.
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