目的 制备负载冬凌草甲素（oridonin，ORI）的聚乙二醇功能化氧化石墨烯（PEGylated graphene oxide，GO-PEG）纳米粒（nanoparticles，NPs），并探讨其对结肠癌的抑制作用。方法 利用酰胺化反应将端基为氨基的四臂聚乙二醇（PEG）连到氧化石墨烯（GO）上，并通过红外光谱（IR）和差示-热重联用热分析仪（TGA）等对其进行表征；再通过物理共混的方法在GO-PEG上负载抗肿瘤药物ORI，紫外光谱（UV）法测其包封率和载药率，MTT法测定载药体系对人结肠癌细胞SW620和HT29的增殖毒性，并建立荷瘤裸鼠模型考察其体内抗肿瘤活性。结果 IR和TGA测定结果表明PEG已成功偶联到GO上，UV法测得ORI-GO-PEG的包封率和载药率分别为95.81%和48.92%，且在各种生理溶液中具有良好的稳定性。体外细胞毒性实验结果表明，与ORI裸药相比，ORI-GO-PEG-NPs对结肠癌细胞的杀伤能力更强。体内抑瘤实验进一步发现，ORI-GO-PEG-NPs可以更好地抑制体内SW620肿瘤的生长。结论 制得的ORI-GO-PEG-NPs具有优良的载药性能和较强的抗结肠癌作用，为今后开发抗肿瘤药物纳米给药系统提供了实验依据。

Objective To prepare PEGylated graphene oxide nanoparticles (GO-PEG-NPs) loaded with oridonin (ORI) and investigate its inhibitory effect on human colon cancer. Methods 4-armed PEG was grafted onto GO via an amidation process and GO-PEG was characterized by IR and TGA. Then, ORI, a widely used cancer chemotherapy drug, was absorbed onto GO-PEG via blending. The encapsulation efficiency and drug loading ratio were measured by UV. The cytotoxicity of ORI-GO-PEG, GO-PEG, and free ORI on SW620 and HT29 human colon cancer cells were evaluated using MTT assay. In vivo anti-tumor activity of ORI-GO-PEG-NPs were evaluated in mice bearing SW620 tumor. Results IR and TGA data indicated that 4-armed PEG was successfully coupled with GO and UV data showed that the encapsulation efficiency and drug loading ratio were 95.81% and 48.92%, respectively. Moreover, ORI-GO-PEG-NPs showed good stability in physiological condition. The results of cytotoxicity test indicated that compared to free ORI, the ORI-GO-PEG-NPs exhibited higher cytotoxicity in SW620 and HT29 cells. Meanwhile, it was confirmed that ORI-GO-PEG-NPs could significantly inhibit the growth of SW620 tumor in vivo compared with ORI. Conclusion The obtained ORI-GO-PEG-NPs displayed excellent drug-loading capacity and better tumor inhibitory effect. These results provided the experimental basis for development of anticancer drug delivery system.

浙江省科技厅院所专项（2015F50065，2014F10033）