纳米粒作为一种新型药物载体在药物传递领域具有广阔前景，但两大不足却阻碍了其临床应用：一，静脉注射后会很快被单核-巨噬细胞系统摄取而从血液循环中清除；二，潜在的纳米毒性。近来研究发现，纳米粒进入血液后会立刻被各种血浆蛋白包裹，从而改变纳米粒所传递的生物信号，这很可能是导致上述两大问题的重要原因。因此，探索如何抑制血 浆蛋白对纳米粒的吸附对开发高效低毒纳米制剂具有重大意义。本课题首次提出通过体外孵育事先将白蛋白以物理作用吸附于纳米粒表面，在没有竞争吸附的作用下形成稳定的白蛋白包衣，从而抑制其它血浆蛋白的吸附，延长循环时间并降低毒性。本课题将研究纳米粒表面性质对白蛋白包衣形成的影响，系统评价白蛋白包衣对血浆蛋白吸附的抑制作用以及对纳米粒理化性质、毒性和体内处置的调节作用，阐明白蛋白包衣作为一种物理手段在保护纳米粒递药系统中的功能，为开发新型高效低毒纳米制剂提供新的思路。

As a novel drug carrier system, nanoparticles (NPs) have a great application potential in drug delivery. However, its clinical use is limited due largely to the following two drawbacks: a) rapid uptake by mononuclear phagocyte system and clearance from blood circulation after intravenous (iv) injection; and b) potential nanotoxicity. It is found recently that NPs will be coated by thousands of plasma proteins immediately after its entry into the blood. As a result, the biological signals delivered by NPs are changed, which is probably the main reason for the above two drawbacks. Therefore, exploring methods to inhibit plasma proteins adsorption onto NPs is essential for developing high-effectiveness and low-toxicity NPs formulations. In this present project, we propose, for the first time, a novel physical strategy to solve the above problems. NPs are coated with albumin via physical adsorption in vitro. The stable albumin coating then acts as a barrier inhibiting the adsorption of other plasma proteins onto NPs after iv injection, leading to a longer circulation time and reduced toxicity. Briefly, in this project, we will investigate the impact of surface properties of NPs on the formation of albumin coating, evaluate the effect of albumin coating on the inhibition of plasma proteins adsorption and on the NPs physicochemical properties, nanotoxicity and in vivo disposition, illuminate the protective effect of albumin coating on the NPs based drug delivery systems, and provide a new idea for developing novel high-effectiveness and low-toxicity NPs formulations.