Amphiphilic polymers (HA-ANI) were prepared by grafting hyaluronic acid (HA) and 6-(2-nitroimidazole)hexylamine (ANI) and then self-assemble in water to form nanoparticles (NPs) that could be loaded with paclitaxel (PTX) and gemcitabine (GEM) by dialysis. Infrared spectroscopy and ¹H-NMR indicated the successful synthesis of HA-ANI. Three different ratios of NPs were prepared by adjusting the ratios of hydrophilic and hydrophobic materials, and the particle size decreased as the ratio of hydrophilic materials increased. When HA:ANI = 2.0:1, the nanoparticles had the smallest size distribution, good stability and near spherical shape and had high drug loading and encapsulation rates. In vitro release experiments revealed that NADPH could accelerate the drug release from NPs. Cellular uptake rate reached 86.50% at 6 h. The toxic effect of dual drug-loaded nanoparticles (P/G NPs) on MDA-MB-231 cells at 48 h was stronger than that of the free drug. The AO/EB double-staining assay revealed that a large number of late apoptotic cells appeared in the P/G NPs group, and the degree of cell damage was significantly stronger than that of the free drug group. In the cell migration assay, the 24 h-cell migration rate of the P/G NPs group was 5.99%, which was much lower than that of the free group (13.87% and 17.00%). In conclusion, MDA-MB-231 cells could effectively take up P/G NPs, while the introduction of the nano-codelivery system could significantly enhance the toxicity of the drug to MDA-MB-231 cells as well as the migration inhibition effect.

通过接枝透明质酸（HA）和6-（2-硝基咪唑）己胺（ANI）制备两亲性聚合物（HA-ANI），然后在水中自组装形成可负载紫杉醇（PTX）的纳米颗粒（NP）和吉西他滨（GEM）通过透析。红外光谱和¹ H-NMR表明HA-ANI成功合成。通过调节亲水材料和疏水材料的比例制备了三种不同比例的纳米粒子，且随着亲水材料比例的增加，纳米粒子的粒径减小。当HA:ANI=2.0:1时,纳米粒粒径分布最小,稳定性好,形状接近球形,载药量和包封率较高。体外释放实验表明NADPH可以加速药物从NPs中的释放。6 h时细胞摄取率达到86.50%。双载药纳米颗粒（P/G NPs）在48小时对MDA-MB-231细胞的毒性作用强于游离药物。AO/EB双染实验显示P/G NPs组出现大量晚期凋亡细胞，且细胞损伤程度明显强于游离药物组。细胞迁移实验中，P/G NPs组24 h细胞迁移率为5.99%，远低于游离组（13.87%和17.00%）。总之，MDA-MB-231细胞可以有效摄取P/G NPs，而纳米共递送系统的引入可以显着增强药物对MDA-MB-231细胞的毒性以及迁移抑制作用。