The increasing nanomedicine usage has raised concerns about their possible impact on human health. Present evaluation strategies for nanomaterials rely on a case-by-case hazard assessment. They take into account material properties, biological interactions, and toxicological responses. Authorities have also emphasized that exposure route and intended use should be considered in the safety assessment of nanotherapeutics. In contrast to an individual assessment of nanomaterial hazards, we propose in the present work a novel and unique evaluation strategy designed to uncover potential adverse effects of such materials. We specifically focus on spherical engineered nanoparticles used as parenterally administered nanomedicines. Standardized assay protocols from the US Nanotechnology Characterization Laboratory as well as the EU Nanomedicine Characterisation Laboratory can be used for experimental data generation. We focus on both cellular uptake and intracellular persistence as main indicators for nanoparticle hazard potentials. Based on existing regulatory specifications defined by authorities such as the European Medicines Agency and the United States Food and Drug Administration, we provide a robust framework for application-oriented classification paired with intuitive decision making. The Hazard Evaluation Strategy (HES) for injectable nanoparticles is a three-tiered concept covering physicochemical characterization, nanoparticle (bio)interactions, and hazard assessment. It is cost-effective and can assist in the design and optimization of nanoparticles intended for therapeutic use. Furthermore, this concept is designed to be adaptable for alternative exposure and application scenarios. To the knowledge of the authors, the HES is unique in its methodology based on exclusion criteria. It is the first hazard evaluation strategy designed for nanotherapeutics.

中文翻译：

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纳米药物的临床前危害评估策略。

越来越多的纳米药物使用引起了人们对其可能对人类健康的影响的担忧。当前的纳米材料评估策略依赖于个案风险评估。它们考虑了材料特性，生物相互作用和毒理学响应。当局还强调，在纳米疗法的安全性评估中应考虑接触途径和预期用途。与对纳米材料危害的单独评估相比，我们在本工作中提出了一种新颖而独特的评估策略，旨在发现此类材料的潜在不利影响。我们特别关注用作胃肠外给药的纳米药物的球形工程纳米颗粒。来自美国纳米技术表征实验室和欧盟纳米医学表征实验室的标准化测定方案可用于实验数据生成。我们专注于细胞摄取和细胞内持久性作为纳米颗粒危害潜能的主要指标。根据欧洲药品管理局和美国食品药品监督管理局等机构定义的现有监管规范，我们为面向应用的分类和直观的决策提供了一个可靠的框架。可注射纳米颗粒的危害评估策略（HES）是一个三层概念，涵盖了理化特性，纳米颗粒（生物）相互作用和危害评估。它具有成本效益，可以帮助设计和优化用于治疗用途的纳米颗粒。此外，此概念旨在适应其他暴露和应用场景。据作者所知，HES在基于排除标准的方法上是独特的。这是专为纳米疗法设计的第一种危害评估策略。