In vivo self-assembled nanomedicine

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 in vivo self-assembly which combines the dynamic and adaptive behavior of self-assembly with internal biological stimuli to construct self-assembled nanomedicine in vivo. In this review, we focus on the transportation process of in vivo 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 in vivo 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 in vivo 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 in vivo 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.