LHRHa与八聚精氨酸共修饰载氟尿嘧啶靶向脂质体的构建及其抗前列腺癌作用  

Preparation of LHRHa and R8 Co-modified 5-FU Loaded Liposome and Its Anti-prostate Cancer Effect

作　　者：杨庆良[1] 夏永华[2] 何岩[3] 张广云[1] 宋歌[1] 

机构地区：[1]河南省安阳市人民医院泌尿外科,安阳455000 [2]新乡医学院第一附属医院皮肤科,新乡453100 [3]新乡医学院第一附属医院泌尿外科,新乡453100

出　　处：《医药导报》2015年第1期30-34,共5页Herald of Medicine

摘　　要：目的构建促黄体激素释放激素类似物(LHRHa)与八聚精氨酸(R8)共修饰载氟尿嘧啶(5-FU)脂质体(LHRHa/R8-LP-5-FU),对其前列腺癌靶向性以及治疗效果进行初步研究。方法采用薄膜分散法制备LHRHa/R8-LP-5-FU,考察其形态、粒径、电位,并通过PC-3前列腺癌细胞定性和定量摄取实验考察其前列腺癌细胞靶向性。采用噻唑蓝(MTT)实验以及肿瘤球实验考察LHRHa/R8-LP-5-FU对PC-3细胞增殖抑制率。结果所制备LHRHa/R8-LP-5-FU粒径为(115.0±15.2)nm,电位为(11.00±2.15)m V,5-FU的包封率(84.5±5.1)%。体外细胞摄取实验表明,PC-3细胞对LHRHa/R8-LP摄取效率分别是R8修饰脂质体(R8-LP)和LHRHa修饰脂质体(LHRHa-LP)2.8和3.2倍(P<0.01)。细胞毒性实验结果显示,以0.9%氯化钠溶液为对照,LP-5-FU、R8-LP-5-FU、LHRHa-LP-5-FU和LHRHa/R8-LP-5-FU对PC-3细胞的增殖抑制率分别为(26.4±4.5)%,(39.5±4.2)%,(48.6±3.5)%和(82.5±4.3)%(P<0.01)。LHRHa/R8-LP-5-FU对肿瘤球的生长抑制作用明显高于其他脂质体。细胞毒性实验结果与细胞摄取实验结果一致。结论 LHRHa与细胞穿膜肽共修饰载5-FU脂质体具有良好的前列腺肿瘤细胞靶向性和抗肿瘤作用,是一种潜在的治疗前列腺癌的高效给药系统。Objective To prepare luteinizing hormone-releasing hormone analogues （LHRHa） and R8 co-modified 5- FU loaded liposome （LHRHa/R8-LP-5-FU） and investigate therapeutic effect towards prostate cancer. Methods The co- modified liposome was prepared by film-ultrasonic method. The appearance, particle size and Zeta potential were evaluated. The cellular uptake by PC-3 cells in vitro was used to evaluate the targeting efficiency. The anti-proliferation activity of LHRHa/RS- LP-5-FU was evaluated by MTr assay. Tumor spheroids were used to evaluate anti-tumor ability of LHRHa/R8-LP-5-FU in vitro. Results The particle diameter of the co-modified liposome was （ 115.0± 15.2） nm with the Zeta potential of （ 11.00± 2.15） mV. The embedding ratio of LHRHa/R8-LP-5-FU was （84.5±5. 1 ）%. The result demonstrated that the ratio of co- modified liposome uptaken by PC-3 were 2.8 and 3.2 times higher than that of RS-LP and LHRHa-LP（ P〈0.01 ）, respectively, and the cell inhibition of LP-5-FU, R8-LP-5-FU, LHRHa-LP-5-FU and LHRHa/R8-LP-5-FU were （ 26.4±4.5 ） % , （ 39.5± 4.2 ） % , （48.6±3.5） % and （ 82.5 ±4.3 ） % （ P〈0. 01 ）, respectively. The inhibition of the growth of tumor sphere by LHRHa/ R-LP-5-FU was obviously higher than that of the other liposome groups. The experimental results of cell toxicity were consistent with the experimental results of cell uptake. Conclusion The co-modified liposome may serve as a promising prostate cancer delivery system for antitumor agents.

关 键 词：促黄体激素释放激素类似物 八聚精氨酸 脂质体 癌 前列腺 

分 类 号：R979.1[医药卫生—药品] R965[医药卫生—药学]