目的 以叶酸-白蛋白作为纳米载体，并包载抗癌药物紫杉醇和纳米银，以达到增加药物毒性和细胞摄取以及提高抗叶酸受体高表达肿瘤的目的。方法 通过紫外吸收法测定牛血清白蛋白（BSA）的平均叶酸结合数，采用自组装法制备纳米粒，并对其形状、粒径、Zeta电位和包封率进行表征；另外在人口腔上皮癌KB细胞模型上考察纳米粒的细胞摄取能力，以及载药纳米粒的体外抗肿瘤的效果。结果 紫外吸收结果表明叶酸-白蛋白的平均叶酸结合数为11个，在电镜下纳米粒呈球形、大小分布均匀，Fa-BSA-AgNP/PTX的粒径为（98.20±3.58）nm，Zeta电位为（-39.90±1.98）mV。细胞摄取实验结果显示叶酸修饰白蛋白纳米粒更易于被KB细胞摄取。细胞毒性和凋亡实验结果表明叶酸的修饰和共载纳米银能够增加药物对肿瘤细胞增殖的抑制能力和促进KB细胞凋亡。结论 制备的纳米粒粒径小，包封率高，可以增强纳米粒被摄取的能力和载药纳米粒的毒性。

Objective Paclitaxel and nanosilver were co-encapsulated into folic acid-albumin nanoparticles to increase the toxicity and uptake of the drug and improve the targeting ability of tumor that highly expressed folic acid (Fa) receptor. Methods The mean Fa binding number of bovine serum albumin (BSA) was determined by ultraviolet absorption method. The nanoparticles were prepared through self-assemble method and then its shape, partical size, Zeta potential, and encapsulation efficiency were characterized with the dynamic light scattering (DLS) and transmission electron microscope (TEM). In addition, the cellular uptake of nanoparticles and the in vitro anti-tumor effect of drug-loaded nanoparticles were investigated on the KB cells model of oral epithelial carcinoma. Results Ultraviolet absorption results showed that the average Fa binding number of Fa-BSA was 11. The nanoparticles were discrete and uniform spheres with the average size of (98.20 ±3.58) nm and Zeta potential of (-39.90 ±1.98) mV. Cellular uptake experiments showed that folate-modified albumin nanoparticles were more easily taken up by KB cells. Cytotoxicity and apoptosis assay indicated that the modification of folic acid and co-loaded nanosilver could increase the inhibition of tumor cell proliferation and promote KB cells apoptosis. Conclusion The prepared nanoparticles have small particle size and high encapsulation efficiency, which can enhance the ability of the nanoparticles to be uptaken and the toxicity of the drug-loaded nanoparticles against tumor cells.

国家重大科学研究计划（“973”）项目“用于脑部肿瘤治疗的新型纳米药物研究”（2013CB932500）