开发紫杉醇(PTX)新制剂一直是业内关注的焦点。基于小分子的纳米药物(SMND)整体由小分子组装形成，具有质量易控、载药量高、工艺简便等独特性质，成为新一代纳米药物研究的热点。如何设计SMND，避免体内调理，同时阐明其体内过程，对于PTX新制剂的开发至关重要。本课题拟构建血液中自动披覆蛋白冠“马甲”的仿生长循环SMND：以对白蛋白具有强亲和力的伊文斯兰为亲水基，VE为疏水基，合成两亲性骨架分子，然后将PTX通过pH敏感键与之连接。前药体外自组装形成SMND，在伊文斯兰介导下，体内快速吸附白蛋白，赋予纳米粒长循环能力和靶向功能，富集于肿瘤部位后，酸性条件下释药，有利于增强PTX的生物利用度，提高疗效。同时，利用FRET染料标记SMND，阐明其体内解离、清除、长循环和组织分布，为SMND的合理设计和优化提供借鉴。该研究对提高SMND成药性，开发升级版PTX新制剂，具有重要意义。

It has drawn great attention to develop novel paclitaxel (PTX) preparations. Small molecule-based nanodrugs (SMND) are composed of small molecule drugs or their derivatives, which possess unique properties of simple composition, easy-to-control quality, high drug loading and economical fabrication. It has shown the potential to be the next generation of nanomedicine. However, how to design SMND of PTX to avoid recognition and clarify its process in vivo remain a great challenge. Taking the advantage of the abundant albumin in blood, a biomimetic stealth SMND was constructed, which can bind endogenous albumin once-injected. First, the amphiphilic molecule was synthesized by using evans blue (EB) as hydrophilic group with high affinity for albumin and VE as hydrophobic group. Then, PTX is connected via a pH-sensitive linker to EB-VE. SMND was formed by self-assembly of prodrug in vitro. After injected into the blood, albumin was absorbed quickly by SMND under the guidance of EB, which endows the SMND with stealth function and tumor targeting ability. When accumulated in the tumor site, free PTX can be released under acidic conditions, which should greatly enhance the bioavailability and efficacy of PTX. Meanwhile, FRET dye labeled SMND was built to study its dissociation, clearance, long circulation and tissue distribution in vivo, which is of great significance for the rational design and optimization of SMND. And this study would lay the foundation for improving the druggability of SMND and developing new PTX preparation better than Abraxane.