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Understanding the In Vivo Fate of Advanced Materials by Imaging

机译：通过成像了解高级材料的体内命运

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摘要

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 applied 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 magnetic resonance imaging and positron emission tomography/computed tomography 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.
机译：工程材料在生物医学应用中普遍存在，从全身药物递送系统到整形外科植入物，它们在多个时间和长度范围内展开。生物学，纳米材料和宏观植入物的疗效和安全性全部由应用于小分子药物的相同的药理学原则决定，该药物的一般原则包括如何影响材料（药代动力学，PK），并相反地如何影响身体（药效学， PD）。成像技术在监测两个过程中起着越来越富富有洞察力的作用，通常同时：诸如磁共振成像和正电子发射断层扫描/计算断层扫描的平移宏观成像模型提供了生物分布和结构或分子反应的全身定量，而离文方法和体内显微镜（滚内）显微镜的光学成像揭示了亚细胞分辨率下的行为。在本文中，作者调查了在系统和本地管理材料的原位行为成像的发展，特别侧重于使用显微镜来理解单个细胞水平的传输，目标接触和下游宿主响应。研究了微观环境影响，受控药物释放，靶分子作用和免疫应答的主题，尤其是由巨噬细胞和其他骨髓细胞介导的。最后，提出了新的成像技术如何推动下一代治疗和医疗器械的有效临床翻译的未来方向。

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