Understanding the in vivo Fate of Advanced Materials by Imaging.

Engineered materials are ubiquitous in biomedical applications ranging from systemic drug delivery systems to orthopedic implants, and their actions unfold across multiple time- and length-scales. The efficacy and safety of biologics, nanomaterials, and macroscopic implants are all dictated by the same general principles of pharmacology as apply to small molecule drugs, comprising how the body affects materials (pharmacokinetics, PK) and conversely how materials affect the body (pharmacodynamics, PD). Imaging technologies play an increasingly insightful role in monitoring both of these processes, often simultaneously: translational macroscopic imaging modalities such as MRI and PET/CT offer whole-body quantitation of biodistribution and structural or molecular response, while ex vivo approaches and optical imaging via in vivo (intravital) microscopy reveal behaviors at subcellular resolution. In this review, the authors survey developments in imaging the in situ behavior of systemically and locally administered materials, with a particular focus on using microscopy to understand transport, target engagement, and downstream host responses at a single-cell level. The themes of microenvironmental influence, controlled drug release, on-target molecular action, and immune response, especially as mediated by macrophages and other myeloid cells are examined. Finally, the future directions of how new imaging technologies may propel efficient clinical translation of next-generation therapeutics and medical devices are proposed.