Abram S-L, Tavernaro I, Johnston L J, Zou S, Resch-Genger U
Division Biophotonics, Federal Institute for Materials Research and Testing (BAM), Richard-Willstaetter-Str. 11, 12489, Berlin, Germany.
Metrology Research Centre, National Research Council Canada (NRC), 100 Sussex Drive, Ottawa, ON, K1A 0R6, Canada.
Anal Bioanal Chem. 2025 May;417(12):2405-2425. doi: 10.1007/s00216-024-05719-6. Epub 2025 Jan 4.
The rational design of engineered nanomaterials (NMs) with improved functionality and their increasing industrial application requires reliable, validated, and ultimately standardized characterization methods for their application-relevant, physicochemical key properties such as size, size distribution, shape, or surface chemistry. This calls for nanoscale (certified) reference materials (CRMs; RMs) and well-characterized reference test materials (RTMs) termed also quality control (QC) samples, assessed, e.g., in interlaboratory comparisons, for the validation and standardization of commonly used characterization methods. Thereby, increasing concerns regarding potential risks of NMs are also addressed and the road for safe and sustainable-by-design concepts for the development of new functional NMs and their use as nanomedicines is paved. With this respect, we will provide an overview of relevant international standardization and regulatory activities, definitions, and recommendations on characterization methods and review currently available organic or inorganic nanoscale CRMs, RMs, and RTMs, including their characterization or certification. In addition, we will highlight typical applications to streamline the regulatory approval process and improve manufacturability including the special challenges imposed by the colloidal nature and sometimes limited stability of NMs. Subsequently, we will critically assess the limitations of currently available nanoscale RMs and RTMs and address the gaps to be filled in the future such as the availability of NMs that come with reference data on properties other than commonly addressed particle size, such as surface chemistry or particle number concentration, or more closely resemble commercially available formulations or address application-relevant matrices.
合理设计具有改进功能的工程纳米材料（NMs）及其不断增加的工业应用，需要针对其与应用相关的物理化学关键特性（如尺寸、尺寸分布、形状或表面化学性质）采用可靠、经过验证并最终实现标准化的表征方法。这就需要纳米级（经过认证的）参考材料（CRMs；RMs）以及经过充分表征的参考测试材料（RTMs，也称为质量控制（QC）样品），例如在实验室间比对中进行评估，以验证和标准化常用的表征方法。由此，人们对NMs潜在风险的日益关注也得到了解决，为开发新型功能性NMs及其作为纳米药物的应用的安全和可持续设计概念铺平了道路。在这方面，我们将概述相关的国际标准化和监管活动、定义以及关于表征方法的建议，并回顾目前可用的有机或无机纳米级CRMs、RMs和RTMs，包括它们的表征或认证。此外，我们将强调典型应用，以简化监管审批流程并提高可制造性，包括NMs的胶体性质以及有时有限的稳定性所带来的特殊挑战。随后，我们将批判性地评估目前可用的纳米级RMs和RTMs的局限性，并指出未来需要填补的空白，例如提供除了通常所关注的粒径之外还具有其他性质参考数据（如表面化学性质或颗粒数浓度）的NMs，或者更类似于市售配方或涉及与应用相关基质的NMs。
