State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
Department of Chemistry, the University of Chicago, Chicago, IL, 60637, USA.
Small. 2023 Jul;19(28):e2207973. doi: 10.1002/smll.202207973. Epub 2023 Mar 27.
The development of smart nanosystems, which could overcome diverse biological barriers of nanomedicine transport, has received intense scientific interest in improving the therapeutic efficacies of traditional nanomedicines. However, the reported nanosystems generally hold disparate structures and functions, and the knowledge of involved biological barriers is usually scattered. There is an imperative need for a summary of biological barriers and how these smart nanosystems conquer biological barriers, to guide the rational design of the new-generation nanomedicines. This review starts from the discussion of major biological barriers existing in nanomedicine transport, including blood circulation, tumoral accumulation and penetration, cellular uptake, drug release, and response. Design principles and recent progress of smart nanosystems in overcoming the biological barriers are overviewed. The designated physicochemical properties of nanosystems can dictate their functions in biological environments, such as protein absorption inhibition, tumor accumulation, penetration, cellular internalization, endosomal escape, and controlled release, as well as modulation of tumor cells and their resident tumor microenvironment. The challenges facing smart nanosystems on the road heading to clinical approval are discussed, followed by the proposals that could further advance the nanomedicine field. It is expected that this review will provide guidelines for the rational design of the new-generation nanomedicines for clinical use.
智能纳米系统的发展能够克服纳米医学输送中的多种生物学障碍，因此受到科学界的极大关注，旨在提高传统纳米药物的治疗效果。然而，已报道的纳米系统通常具有不同的结构和功能，而涉及的生物学障碍的相关知识通常较为分散。因此，非常有必要对生物学障碍进行总结，并梳理智能纳米系统如何克服这些生物学障碍，以指导新一代纳米药物的合理设计。本综述从讨论纳米医学输送中存在的主要生物学障碍开始，包括血液循环、肿瘤积累和渗透、细胞摄取、药物释放和反应。概述了智能纳米系统克服生物学障碍的设计原则和最新进展。纳米系统的指定物理化学性质可以决定其在生物环境中的功能，如蛋白吸收抑制、肿瘤积累、渗透、细胞内化、内涵体逃逸和控制释放，以及对肿瘤细胞及其驻留的肿瘤微环境的调节。讨论了智能纳米系统在走向临床批准的道路上面临的挑战，并提出了进一步推动纳米医学领域发展的建议。预计本综述将为新一代临床应用纳米药物的合理设计提供指导。
