Over the past few decades, nanoengineered particles have gained increasing interest for applications in the biomedical realm, including diagnosis, imaging, and therapy. When functionalized with targeting ligands, these particles have the potential to interact with specific cells and tissues, and accumulate at desired target sites, reducing side effects and improve overall efficacy in applications such as vaccination and drug delivery. However, when targeted particles enter a complex biological environment, the adsorption of biomolecules and the formation of a surface coating (e.g., a protein corona) changes the properties of the carriers and can render their behavior unpredictable. For this reason, it is of importance to consider the potential challenges imposed by the biological environment at the early stages of particle design. This review describes parameters that affect the targeting ability of particulate drug carriers, with an emphasis on the effect of the protein corona. We highlight strategies for exploiting the protein corona to improve the targeting ability of particles. Finally, we provide suggestions for complementing current in vitro assays used for the evaluation of targeting and carrier efficacy with new and emerging techniques (e.g., 3D models and flow‐based technologies) to advance fundamental understanding in bio‐nano science and to accelerate the development of targeted particles for biomedical applications.

中文翻译：

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复杂生物介质中的粒子靶向

在过去的几十年中，纳米工程粒子对生物医学领域的应用越来越感兴趣，包括诊断，成像和治疗。当使用靶向配体进行功能化时，这些颗粒具有与特定细胞和组织相互作用的潜力，并且可以在所需的靶位点积聚，从而减少了副作用，并提高了在诸如疫苗接种和药物递送等应用中的整体功效。但是，当目标粒子进入复杂的生物环境时，生物分子的吸附和表面涂层（例如蛋白质电晕）的形成会改变载体的性质，并使其行为无法预测。因此，在粒子设计的早期阶段考虑生物环境所带来的潜在挑战非常重要。这篇综述描述了影响颗粒状药物载体靶向能力的参数，重点是蛋白质电晕的作用。我们重点介绍了利用蛋白质电晕来提高粒子靶向能力的策略。最后，我们提供了一些建议，以利用新兴技术（例如3D模型和基于流的技术）补充当前用于评估靶点和载体功效的体外测定，以增进对生物纳米科学的基本了解并加速发展用于生物医学应用的目标颗粒。