Nanomedicines improve drug bioavailability, the dose–response relationship, targeting ability, efficacy and safety compared to conventional freely administered drugs. Nonetheless, despite their success as carriers for SARS-CoV-2 vaccines, clinical use of nanomedicines is still limited, probably caused by mismatches between animal models and humans. In this Review, we propose that improving blood circulation, biodistribution and tissue accessibility could help improve the clinical translation of nanomedicines. Specifically, we emphasize control of the pharmacokinetics relevant to the administration route, therapeutic targets in tissues and cells, and the drug payloads. Furthermore, we analyse the clearance and distribution of nanomedicines in preclinical and clinical studies, highlighting the biological barriers determining their in vivo performance. Finally, we present engineering strategies, such as size tuning, active targeting for transcytosis, external stimuli and biological shifts, to overcome these barriers.

与传统的自由给药药物相比，纳米药物提高了药物的生物利用度、剂量反应关系、靶向能力、功效和安全性。尽管如此，尽管纳米药物作为 SARS-CoV-2 疫苗的载体取得了成功，但其临床应用仍然有限，这可能是由于动物模型与人类之间的不匹配造成的。在这篇综述中，我们提出改善血液循环、生物分布和组织可及性有助于改善纳米药物的临床转化。具体来说，我们强调控制与给药途径、组织和细胞中的治疗靶点以及药物有效负载相关的药代动力学。此外，我们分析了纳米药物在临床前和临床研究中的清除和分布，强调了决定其体内性能的生物屏障。最后，我们提出了工程策略，例如尺寸调整、转胞吞作用的主动靶向、外部刺激和生物转变，以克服这些障碍。