CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.
Acc Chem Res. 2013 Mar 19;46(3):761-9. doi: 10.1021/ar2003336. Epub 2012 Jun 21.
Before researchers apply nanomaterials (NMs) in biomedicine, they need to understand the blood circulation and clearance profile of these materials in vivo. These qualities determine the balance between nanomaterial-induced activity and unwanted toxicity. NMs have heterogeneous characteristics: they combine the bulk properties of solids with the mobility of molecules, and their highly active contact interfaces exhibit diverse functionalities. Any new and unexpected circulation features and clearance patterns are of great concern in toxicological studies and pharmaceutical screens. A number of studies have reported that NMs can enter the bloodstream directly during their application or indirectly via inhalation, ingestion, and dermal exposure. Due to the small size of NMs, the blood can then transport them throughout the circulation and to many organs where they can be stored. In this Account, we discuss the blood circulation and organ clearance patterns of NMs in the lung, liver, and kidney. The circulation of NMs in bloodstream is critical for delivery of inhalable NMs to extrapulmonary organs, the delivery of injectable NMs, the dynamics of tissue redistribution, and the overall targeting of drug carriers to specific cells and organs. The lung, liver, and kidney are the major distribution sites and target organs for NMs exposure, and the clearance patterns of NMs in these organs are critical for understanding the in vivo fate of NMs. Current studies suggest that multiple factors control the circulation and organ clearance of NMs. The size, shape, surface charge, surface functional groups, and aspect ratio of NMs as well as tissue microstructures strongly influence the circulation of NMs in bloodstream, their site-specific extravasation, and their clearance profiles within organs. Therefore structure design and surface modification can improve biocompatibility, regulate the in vivo metabolism, and reduce the toxicity of NMs. The biophysicochemical interactions occurring between NMs and between NMs and the biological milieu after the introduction of NMs into living systems may further influence the blood circulation and clearance profiles of NMs. These interactions can alter properties such as agglomeration, phase transformations, dissolution, degradation, protein adsorption, and surface reactivity. The physicochemical properties of NMs change dynamically in vivo thereby making the metabolism of NMs complex and difficult to predict. The development of in situ, real-time, and quantitative techniques, in vitro assays, and the adaptation of physiologically-based pharmacokinetic (PBPK) and quantitative structure-activity relationship (QNSAR) modeling for NMs will streamline future in vivo studies.
在研究人员将纳米材料 (NMs) 应用于生物医学之前，他们需要了解这些材料在体内的血液循环和清除情况。这些特性决定了纳米材料诱导的活性与不必要毒性之间的平衡。NMs 具有不均匀的特性：它们结合了固体的体相性质和分子的迁移性，其高活性的接触界面表现出多样化的功能。在毒理学研究和药物筛选中，任何新的和意外的循环特征和清除模式都非常令人关注。有许多研究报告称，NMs 在应用过程中可以直接进入血液，或者通过吸入、摄入和皮肤暴露间接进入血液。由于 NMs 的尺寸较小，血液可以将它们运输到整个循环系统，并运输到许多可以储存它们的器官中。在本综述中，我们讨论了 NMs 在肺、肝和肾中的血液循环和器官清除模式。NMs 在血液中的循环对于可吸入 NMs 向肺外器官的输送、可注射 NMs 的输送、组织再分布的动力学以及药物载体对特定细胞和器官的整体靶向都至关重要。肺、肝和肾是 NMs 暴露的主要分布部位和靶器官，NMs 在这些器官中的清除模式对于理解 NMs 的体内命运至关重要。目前的研究表明，多种因素控制着 NMs 的血液循环和器官清除。NMs 的尺寸、形状、表面电荷、表面官能团和纵横比以及组织微结构强烈影响 NMs 在血液中的循环、它们在特定部位的渗出以及它们在器官内的清除情况。因此，结构设计和表面改性可以提高 NMs 的生物相容性、调节体内代谢并降低 NMs 的毒性。NMs 与生物环境之间以及 NMs 引入活系统后发生的生物物理化学相互作用可能进一步影响 NMs 的血液循环和清除情况。这些相互作用可以改变团聚、相转变、溶解、降解、蛋白质吸附和表面反应性等性质。NMs 的物理化学性质在体内动态变化，从而使 NMs 的代谢变得复杂且难以预测。原位、实时和定量技术的发展、体外测定以及基于生理的药代动力学 (PBPK) 和定量构效关系 (QSAR) 建模的适应将简化未来的体内研究。
