The emergence of nanomedicine improved the pharmacokinetics of conventional therapeutic agents through ensuring its optimal biodistribution and targeted accumulation. However, the biological barriers along with the alteration on stability and surface properties of nanomedicine during transportation hinder its clinical translation. In order to address those challenges, we propose a strategy of self-assembly which combines the dynamic and adaptive behavior of self-assembly with internal biological stimuli to construct self-assembled nanomedicine . In this review, we focus on the transportation process of self-assembled nanomedicine, in which we mainly discuss the specific molecular design and its self-assembling process that influence the targeted accumulation towards disease sites. The transportation process of self-assembled nanomedicine can be described as four cascade processes including the targeting, penetration, accumulation and clearance. Frist, we will provide an update on the construction and working mechanism of self-assembled nanomedicine. Then, we summarize the molecular designing strategies and discuss its self-assembling process for improving the penetration depth, targeted accumulation and optimal clearance of nanomachines in detail. More importantly, we highlight the influence of the molecular state on its transportation process to emphasize the contribution of molecular state difference of self-assembled nanomedicine between pathological site and other organs on its targeted accumulation and reduced toxicity. In addition, we summarize its biomedical applications to manifest its potential on clinical translation. Finally, we briefly described our perspective on molecular design, dynamic self-assembling process and the relationship between nanostructure and its biological effects to highlight those challenges in this field.

中文翻译：

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体内自组装纳米医学

纳米药物的出现通过确保其最佳的生物分布和靶向积累改善了传统治疗药物的药代动力学。然而，生物屏障以及纳米药物在运输过程中稳定性和表面性质的改变阻碍了其临床转化。为了应对这些挑战，我们提出了一种自组装策略，将自组装的动态和自适应行为与内部生物刺激相结合，构建自组装纳米医学。在这篇综述中，我们重点关注自组装纳米药物的运输过程，其中我们主要讨论影响疾病部位靶向积累的特定分子设计及其自组装过程。自组装纳米药物的运输过程可以描述为四个级联过程，包括靶向、渗透、积累和清除。首先，我们将介绍自组装纳米医学的构建和工作机制的最新情况。然后，我们总结了分子设计策略，并详细讨论了其自组装过程，以提高纳米机器的渗透深度、靶向积累和最佳清除。更重要的是，我们强调了分子状态对其运输过程的影响，以强调自组装纳米药物在病理部位和其他器官之间的分子状态差异对其靶向积累和降低毒性的贡献。此外，我们总结了其生物医学应用，以展示其在临床转化方面的潜力。最后，我们简要描述了我们对分子设计、动态自组装过程以及纳米结构与其生物效应之间的关系的看法，以强调该领域的挑战。