miR-34a和米铂共载阳离子脂质体的构建及抗肿瘤活性研究  

Construction and anti-tumor activity of miR-34a and miriplatin co-loaded cationic liposomes

作　　者：王丹[1] 孟月 王晓葳 王雪蕾 王晓波 苏嘉怡 夏桂民[1] WANG Dan;MENG Yue;WANG Xiao-wei;WANG Xue-lei;WANG Xiao-bo;SU Jia-yi;XIA Gui-min(Department of Pharmaceutics,Institute of Medicinal Biotechnology,Chinese Academy of Medical Science&Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国医学科学院北京协和医学院医药生物技术研究所制剂研究室,北京100050

出　　处：《中国医药生物技术》2024年第5期410-419,共10页Chinese Medicinal Biotechnology

基　　金：中国医学科学院医学与健康科技创新工程(2021-I2M-1-026、2021-I2M-1-070);中央高校基本科研业务费专项(3332023049)。

摘　　要：目的 构建共载miR-34a和米铂阳离子脂质体,以协同增效,用于肿瘤的化疗。方法 采用薄膜分散法制备米铂阳离子脂质体(MCL),将MCL与miR-34a共孵育,构建共载miR-34a和米铂的阳离子脂质体(MCL/miR-34a)。以粒径及多分散系数、电位、米铂含量和抗肿瘤活性为指标,对辅助磷脂(DOPE、DOPC、DMPC、DSPC、PC-98T)的种类、阳离子磷脂DOTAP/DOPE比、N/P、DSPE-mPEG2000及胆固醇用量进行筛选;选用磺酰罗丹明B染色法在细胞(人乳腺癌细胞系MDA-MB-231、人肝癌细胞系HepG2、人口腔表皮样癌细胞系KB和人胰腺癌细胞系As PC-1)水平评价MCL/miR-34a的抗肿瘤活性。结果 构建的MCL/miR-34a粒径均匀[(200±23)nm]且分布窄(PDI=0.242±0.01)、电位适宜[(45±8)m V]、包封率高(miR-34a的包封率99.2%,米铂的包封率99.8%),细胞水平上抗肿瘤活性显著优于单药米铂或mi R-34a。结论 成功构建的MCL/miR-34a可显著提高miR-34a和米铂的体外抗肿瘤活性,为核酸药物与小分子化疗药物共同递送提供新策略。Objective The aim of this study was to develop cationic liposomes capable of co-delivering miR-34a and miriplatin for a synergistic anticancer effect in cancer treatment.Methods Miriplatin loaded cationic liposome(MCL)was prepared using the thin film dispersion method,while the co-incubation method was used to prepare miR-34a and miriplatin co-loaded cationic liposome(MCL/miR-34a).Based on particle size,polydispersion coefficient(PDI),Zeta potential,concentration of miriplatin,liposomal formulationwere optimized,including kinds of helper phospholipids(DOPE,DOPC,DMPC,DSPC,PC-98T),the molar ratio of cationic phospholipid DOTAP to DOPE,the ratio of N/P,the amount of DSPE-mPEG2000 and cholesterol.The antitumor effect of MCL/miR-34a on the proliferation of MDA-MB-231,HepG2,KB and AsPC-1 cells was evaluated using Rhodamine B method.Results Through prescription optimization,MCL/miR-34a was successfully prepared with uniform particle size(200 nm±23 nm),narrow distribution(PDI=0.242±0.01),suitable potential(45 mV±8 mV),and high encapsulation rate(99.2%of miR-34a,99.8%of miriplatin).In comparison to monotherapy with either miR-34a or miriplatin alone,MCL/miR-34a significantly improved the anti-tumor efficacy on four tumor cell lines with a synergistic antitumor effect.Conclusion The findings indicate that MCL/miR-34a can significantly improve the effectiveness of antitumor treatment,and may function as an innovative nano delivery system for co-administration of nucleic acid drugs and chemotherapeutic drugs.

关 键 词：阳离子脂质体 米铂 MIR-34A 抗肿瘤活性 

分 类 号：R943[医药卫生—药剂学]