白蛋白的两个基本特质（即载药功能和信号识别功能）使其成为非常有潜力的递药载体。然而，除FDA批准的上市产品Abraxane以外，其它基于白蛋白的递药系统几乎只利用了信号识别功能，白蛋白自身强大的载药功能往往被忽略。白蛋白空间结构中含有六个疏水腔，但正常情况下只有一个能结合药物，导致很低的载药量。本项目提出，利用变性剂打开白蛋白内部空间，暴露所有疏水腔，以便与大量药物分子充分结合，从而显著提高载药量，最后通过复性恢复白蛋白空间结构并形成复性白蛋白-药物复合物这一全新的载药系统。该系统不仅可以保持白蛋白的识别功能，还可以充分利用其载药功能，是一种利用白蛋白构建新型递药系统的全新构思。本项目将对白蛋白整个变性-增溶-复性过程进行全面的表征，并对复性白蛋白-药物复合物的长循环特性、肿瘤靶向性、药效、安全性和成药性进行系统评价，为研发兼备一定创新性和转化潜能的新型缓控释递药系统提供新的思路。

Drug-loading capacity and biological signal recognition, two basic characteristics of albumin, make it a potential carrier for drug delivery. However, except the FDA approved Abraxane, almost all the other albumin-based drug delivery systems only utilize the signal-recognition function of albumin. The great drug-loading potential of albumin is always ignored. Basically, there are six hydrophobic domains in the structure of albumin, but only one of which can be used for drug loading under normal conditions, leading to a very low drug-loading capacity. In this project, we propose to open the inner space of albumin via denaturation and expose all the hydrophobic domains. As such, a lot of drug molecules can bind to the unfolded albumin, resulting in a significantly enhanced drug-loading. After renaturation, a novel drug delivery system based on the refolded albumin-drug complex can be generated. This novel system not only maintains the recognition function of albumin, but also extensively utilize its drug-loading potential. In this project, we will systematically characterize the whole process of albumin denaturation-solubilization-renaturation in forming the refolded albumin-drug complex and evaluate its long-circulation effect, tumor targeting capacity, antitumor efficacy, safety and druggability, aiming at providing a new idea for the development of the novel controlled drug delivery systems that have both innovational and translational potentials.