摘要
目的制备改善肿瘤缺氧耐药的血红蛋白-紫杉醇脂质体。方法采用薄膜法制备血红蛋白-紫杉醇脂质体,通过纳米粒度仪考察其粒径、Zeta电位、多分散系数,通过高效液相色谱仪检测其包封率,并通过体外细胞实验评价其与肿瘤细胞的相互作用。结果血红蛋白-紫杉醇脂质体的最优制备条件为:磷脂总量为36 mM,DPPC∶DOPE∶胆固醇摩尔比为7∶2∶1,紫杉醇用量为3 mg,水化介质为3 mg·mL^(-1)Hb-PBS溶液,水化温度为室温,水化时间为0.5 h;平均粒径为(189.17±8.22)nm,多分散系数为0.14±0.023,紫杉醇包封率为(58.27±2.55)%,血红蛋白含量为(0.63±0.05)mg·mL^(-1)。体外细胞实验中,血红蛋白-紫杉醇脂质体对肿瘤细胞的杀伤作用约为紫杉醇脂质体的1.5倍、被肿瘤细胞摄取量约为紫杉醇脂质体的1.2倍及ROS生成量约为紫杉醇脂质体的1.8倍。结论制备了血红蛋白-紫杉醇脂质体,通过细胞实验证明其能通过改善缺氧、增加ROS产生促进肿瘤细胞凋亡,有望为肿瘤缺氧导致的耐药抵抗提供安全有效的新方法。
Objective To prepare liposomes encapsulate hemoglobin and paclitaxel(LEHP)to improve tumor hypoxia resistance.Methods LEHP were prepared by thin-film method,and the particle size,Zeta potential and polydispersity were investigated by nanoparticle size analyzer,and encapsulation efficiency was investigated by high performance liquid chromatography,and the interaction between the liposomes and tumor cells was evaluated by in vitro cell experiments.Results The optimal preparation conditions of LEHP was as follows:total phospholipid 36 mM,DPPC∶Dope∶cholesterol molar ratio 7∶2∶1,paclitaxel 3 mg,hydrated with 3 mg·mL^(-1)Hb-PBS for 30 min at room temperature;The average particle size was(189.17±8.22)nm,polydispersity was 0.14±0.023,paclitaxel encapsulation efficiency was(58.27±2.55)%,hemoglobin content was(0.63±0.05)mg·mL^(-1).In vitro cell experiments,the killing effect of LEHP was about 1.5 times that of LEP,about 1.2 times that of LEP,and ROS production was about 1.8 times that of LEP.The optimal preparation conditions of LEHP was as follows:total phospholipid 36 mM,DPPC:DOPE:cholesterol molar ratio 7∶2∶1,paclitaxel 3 mg,hydrated with 3 mg·mL^(-1)Hb-PBS for 30 min at room temperature.The average particle size was(189.17±8.22)nm,polydispersity was 0.14±0.023,paclitaxel encapsulation efficiency was(58.27±2.55)%,hemoglobin content was(0.63±0.05)mg·mL^(-1).In vitro cell experiments,the killing effect of LEHP on tumor cells,the amount of ROS produced and the uptake by tumor cells were higher than those of LEP.Conclusion The preparation conditions of LEHP was optimized,and cell experiments showed that LEHP can promote tumor cell apoptosis by improving hypoxia and increasing ROS production,which is expected to provide a safe and effective new method for drug resistance caused by tumor hypoxia.
作者
游训仪
朱珂慧
肖晶
吴嘉康
郑诗凡
张阿龙
钟锐
王红
曹晔
刘嘉馨
YOU Xunyi;ZHU Kehui;XIAO Jing;WU Jiakang;ZHENG Shifan;ZHANG Along;ZHONG Rui;WANG Hong;CAO Ye;LIU Jiaxin(Institute of Blood Transfusion,Chinese Academy of Medical Sciences&Peking Union Medical College,Chengdu 610052,China;Cancer Hospital&Institute,Sichuan Cancer Center,Affiliated Cancer Hospital of University of Electronic Science and Technology of China)
出处
《中国输血杂志》
CAS
2024年第3期297-303,共7页
Chinese Journal of Blood Transfusion
基金
中国医学科学院医学与健康科技创新工程项目“血液安全保障及新产品技术研究”(2021-I2M-1-060)
四川省科技创新苗子工程(MZGC20230047)。
