目的 制备乳糖酸（LA）修饰聚酰胺-胺树枝状大分子（PAMAM）接枝白藜芦醇（Res）的纳米颗粒，并进行体外评价。方法 采用发散法合成G3.0 PAMAM，将末端部分羧基化（PAMAM-COOH），经酯化反应键合Res、酰胺化反应接枝LA在载体表面，制备LA-PAMAM-Res纳米颗粒，用核磁共振氢谱（¹H-NMR）、红外光谱（IR）进行表征；LA-PAMAM-Res物理包载Res制备LA-PAMAM-Res/Res纳米颗粒，并用透析法检测其包封率；HPLC检测2种纳米颗粒的载药量，激光粒度分析法考察其粒径，透析法测定其体外药物释放性能，溶血性实验评价其生物安全性；MTT法考察PAMAM、PAMAM-COOH、Res、LA-PAMAM-Res和LA-PAMAM-Res/Res的细胞毒性及抗癌活性。结果 成功制备了LA-PAMAM-Res和LA-PAMAM-Res/Res纳米颗粒。LA-PAMAM-Res/Res的包封率为（75.1±2.2）%，LA-PAMAM-Res和LA-PAMAM-Res/Res的载药量分别为（7.2±0.9）%和（18.4±1.1）%，粒径分别为（126.3±3.4）nm和（251.0±15.7）nm，72 h时体外药物释放度分别为（23.83±0.43）%和（35.28±0.72）%，溶血率均低于5%，且载体PAMAM-COOH比PAMAM具有较小的细胞毒性，LA-PAMAM-Res和LA-PAMAM-Res/Res仍具有抑制肿瘤增殖活性。结论 制备了能使药物缓慢释放、生物相容性良好、低细胞毒性和具有抗癌活性的LA-PAMAM-Res和LA-PAMAM-Res/Res纳米颗粒，且LA-PAMAM-Res/Res进一步提高了Res的载药量。

Objective To prepare resveratrol (Res) nanoparticles grafted with polyamide-amine dendrimer (PAMAM) modified by lactose acid (LA) and evaluate them in vitro. Methods After partial carboxylation of G3.0 PAMAM terminal (PAMAM-COOH) which synthesized by divergence method. Res was bonded through esterification reaction and LA was grafted on the surface of the carrier through amidation reaction. Nuclear magnetic resonance (¹H-NMR) and infrared spectroscopy (IR) were used for characterization. La-PAMAM-Res/Res nanoparticles were prepared by physical encapsulation using LA-PAMAM-Res and Res, and the encapsulation rate was detected by dialysis method. The drug load of the two kinds of nanoparticles was detected by high performance liquid chromatography (HPLC), the particle size was investigated by laser particle size analysis method, the drug release performance in vitro was determined by dialysis method, and the biosafety was evaluated by hemolytic experiment. The cytotoxicity and anticancer activity of PAMAM, PAMAM-COOH, Res, LA-PAMAM-Res and LA-PAMAM-Res/Res were investigated by MTT assay. Results LA-PAMAM-Res and La-PAMAM-Res/Res nanoparticles were prepared. The encapsulation rate of LA-PAMAM-Res/Res was (75.1±2.2)%, the drug loading rates of LA-PAMAM-Res and LA-PAMAM-Res/Res were (7.2±0.9)% and (18.4±1.1)%, respectively. The particle size was (126.3±3.4) nm and (251.0±15.7) nm, respectively. After 72 h, the drug release in vitro was (23.83±0.43)% and (35.28±0.72)%, respectively. The hemolysis rate of both nanoparticles was less than 5%, and the carrier PAMAM-COOH showed less cytotoxicity than PAMAM, and both LA-PAMAM-Res and LA-PAMAM-Res/Res maintained anti-tumor proliferative activity. Conclusion LA-PAMAM-Res and LA-PAMAM-Res/Res nanoparticles with sustained drug release, good biocompatibility, low cytotoxicity and anticancer activity were prepared, and LA-PAMAM-Res/Res increased the drug load of Res.

R283.6

国家自然科学基金资助项目（21302040）