酸响应性黄芩苷脂质体抑制肿瘤细胞增殖及其免疫增敏的研究  

Inhibitory effects of acid responsive baicalin liposomes on tumor cell proliferation and immune sensitization

作　　者：刘政翰 张彦龙[1] 曾伟民[1] 刘洋[1] 赵丹丹[1] 贾向前 LIU Zhenghan;ZHANG Yanlong;ZENG Weimin;LIU Yang;ZHAO Dandan;JIA Xiangqian(Engineering Research Center of Agricultural Microbiology Technology,Ministry of Education&Heilongjiang Provincial Key Laboratory of Ecological Restoration and Resource Utilization for Cold Region&Key Laboratory of Microbiology,College of Heilongjiang Province&School of Life Sciences,Heilongjiang University,Harbin 150080,China)

机构地区：[1]黑龙江大学生命科学学院,农业微生物技术教育部工程研究中心,黑龙江省寒地生态修复与资源利用重点实验室,黑龙江省普通高校微生物重点实验室,黑龙江哈尔滨150080

出　　处：《沈阳药科大学学报》2024年第9期1236-1243,1253,共9页Journal of Shenyang Pharmaceutical University

基　　金：黑龙江省高校基本科研业务费黑龙江大学专项资金项目(2021KYYWF0046);黑龙江省高校基本科研业务费黑龙江大学专项资金项目(2022KYYWF1078);黑龙江省博士后面上项目(LBHZ22040)。

摘　　要：目的制备一种酸响应性负载黄芩苷的免疫脂质体(baicalin-liposome-1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(2-ethyl-2-oxazoline,BA-LP-PEOz),旨在利用肿瘤特异性的药物递送和化疗增敏作用,提高黄芩苷的抗肿瘤治疗效率,从而实现高效且不良反应少的治疗目标。方法负载黄芩苷的免疫脂质体由薄膜分散法制备而成,并测定该脂质体的理化性质,同时采用肺癌A549细胞进行体外细胞生长抑制评价,采用RAW264.7巨噬细胞进行体外细胞生长增殖评价。结果BA-LP-PEOz的包封率为(84.3±0.3)%,粒径为(135±5)nm,电位为(-14.9±1.4)mV。当选择合适的给药浓度(黄芩苷质量浓度为100μg·mL^(-1))时,BA-LP-PEOz不仅对A549肺癌细胞具有较强的直接杀伤作用,也可以促进RAW264.7巨噬细胞的增殖,增强巨噬细胞极化为M1型。结论BA-LP-PEOz使黄芩苷发挥了化疗及免疫治疗肿瘤的双重功效,提高黄芩苷的抗肿瘤治疗效率。Objective An acid-responsive baicalin-immunoliposome(baicalin-liposome-1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(2-ethyl-2-oxazoline,BA-LP-PEOz,BA-LP-PEOz)was synthesized to enhance the antitumor therapeutic efficacy of baicalin.By leveraging tumor-specific drug delivery mechanisms and chemosensitization processes,this formulation aims to achieve high therapeutic effect with minimal adverse effects.Methods Baicalin-loaded immunoliposomes were synthesized using the film dispersion method,and the physicochemical characteristics of the liposomes were assessed.In vitro evaluations of cell growth inhibition were conducted using lung cancer A549 cells,while cell growth proliferation assay was performed using RAW264.7 macrophages.Results The encapsulation rate of BA-LP-PEOz was determined to be(84.3±0.3)%,with a particle size of(135±5)nm and a Zeta potential of(-14.9±1.4)mV.BA-LP-PEOz exhibited potent direct cytotoxic effects on A549 cells at the optimal administration concentration(BA mass concentration of 100μg·mL^(-1)).and showed the ability to promote proliferation in RAW264.7 macrophages and enhance macrophage polarization towards the M1 phenotype.Conclusion BA-LP-PEOz can improve the anti-tumor therapeutic efficiency of BA by playing the dual roles of chemotherapy and immunotherapy.

关 键 词：黄芩苷 肿瘤微球 脂质体 巨噬细胞 

分 类 号：R94[医药卫生—药剂学] R96[医药卫生—药学]