经iRGD修饰胡桃醌-紫杉醇靶向纳米粒子的制备及其对人骨肉瘤细胞Saos-2的抑制作用

Preparation and antitumor activity of iRGD modified naonoparticles loaded with juglone and paclitaxel against human osteosarcoma cell line Saos-2

目的构建经iRGD修饰的胡桃醌(juglone,Jug)-紫杉醇(paclitaxel,PTX)靶向纳米粒子(nanoparticles,NPs),并评价其对人骨肉瘤细胞Saos-2的抑制作用。方法通过乳化法制备iRGD-PLGA-(Jug,PTX)-NPs,并评价其材料特性、载药能力和体外释放结果。利用荧光显微镜观察iRGD-PLGA-(Jug,PTX)-NPs体外细胞摄取情况,再通过MTT法比较各组对Saos-2细胞的增殖抑制作用。结果①在Jug:PTX=0.1 mg:0.1 mg,iRGD-PLGA=1 mg条件下,成功制备iRGD-PLGA-(Jug,PTX)-NPs。②透射电镜下可见,纳米粒子为大小均一的类球形,粒径为233.3 nm,Jug载药率为8.68%,包封率为31.87%,PTX载药率为8.98%,包封率为30.18%;③体外药物释放显示,前24 h中为突释,随后为缓释,96 h后Jug累积释放为(72.108±1.243)%,PTX为(69.980±3.626)%;④细胞摄取实验显示,iRGD修饰的纳米粒子较无修饰粒子进入细胞更多;⑤MTT结果显示,Jug和PTX均可抑制Saos-2细胞增殖,且呈现出剂量依赖性。药物处理24 h后,裸药组抑制率明显高于其他组,而在48 h后,iRGD-PLGA-(Jug,PTX)-NPs抑制率高于裸药组。结论iRGD-PLGA-(Jug,PTX)-NPs稳定性较好,包载药物表现出先突释后缓释的现象,iRGD修饰可增强肿瘤靶向穿透性,提升疗效。

Objective To construct the iRGD modified nanoparticles(NPs)loaded with Juglone(Jug)and paclitaxel(PTX)and evaluate their inhibitory effect on human osteosarcoma cell line Saos-2.Methods iRGD-PLGA-(Jug,PTX)NPs were prepared by emulsification method,and their material properties,drug loading capacity,and in vitro release results were evaluated.The uptake of iRGD-PLGA-(Jug,PTX)-NPs in vitro was observed using a fluorescence microscope,then the inhibitory effects of each group on the proliferation of Saos-2 cells were compared using MTT method.Results①Under the conditions of Jug:PTX=0.1 mg:0.1 mg,iRGD-PLGA=1 mg,iRGD-PLGA-(Jug,PTX)-NPs were successfully prepared.②Under transmission electron microscopy,the size of the nanoparticles was uniform,with a particle size of 233.3 nm.The drug loading rate of Jug was 8.68%,the encapsulation rate was 31.87%,the drug loading rate of PTX was 8.98%,and the encapsulation rate was 30.18%.③In vitro drug release experiment displayed that nanoparticles exhibited slow release characteristics.After 96 hours,the cumulative release of Jug was 72.108±1.243%,and the PTX was(69.980±3.626)%.④Cell uptake experiments showed that iRGD modified nanoparticles entered cells more frequently than unmodified particles.⑤The MTT results showed that both Jug and PTX inhibited the proliferation of Saos-2 cells in a dose-dependent manner.After 24 hours of drug treatment,the inhibition rate of the naked drug group was significantly higher than that of the other groups,while after 48 hours,the inhibition rate of iRGD-PLGA-(Jug,PTX)-NPs was higher than that of the naked drug group.Conclusion iRGD-PLGA-(Jug,PTX)NPs have good stability,and the loaded drug bears slow release characteristics,and the iRGD modification has significant inhibitory effect on human osteosarcoma cell line Saos-2.