甘露糖修饰的脂质体共同递送人乳头瘤病毒16 E7多肽和佐剂CpG-寡脱氧核苷酸抗宫颈癌的作用及机制研究  

Anti-cervical cancer effect and mechanism study of mannose-modified liposome co-delivering human papillomavirus 16 E7 polypeptide and CpG oligodeoxynucleotides

作　　者：王欢 王雪莲 车玉鑫 马壮 WANG Huan;WANG Xue-lian;CHE Yu-xin;MA Zhuang(Jinzhou Medical University,Liaoning 121001,China)

机构地区：[1]锦州医科大学,辽宁锦州121001

出　　处：《中国妇幼保健》2023年第23期4675-4679,共5页Maternal and Child Health Care of China

基　　金：辽宁省自然科学基金项目(2021-MS-322)。

摘　　要：目的 构建装载人乳头瘤病毒(HPV)16 E7多肽和佐剂CpG-寡脱氧核苷酸(ODN)的甘露糖修饰的脂质体,在局部晚期宫颈癌小鼠模型中评估接种该疫苗后的效果。方法 研究时间为2022年3—11月。选取6~8周龄的24只雌性C57BL/6小鼠,建立小鼠宫颈癌模型,构建装载HPV16 E7多肽和佐剂CpG-ODN的甘露糖修饰的脂质体,小鼠肿瘤体积达到200 mm~3时接种该疫苗,采用流式细胞术检测疫苗对小鼠免疫功能的影响。结果 透射电镜下,Lip E7/CpG显示出球形结构,负染色后,脂质体大小在60~120 nm的直径范围内变化,动态光散射测量脂质体直径为(122.21±8.37)nm。在(4±2)℃条件下储存,7 d内Lip E7/CpG均能保持良好的稳定性。尤其是粒径和EE在7 d内几乎没有变化,确保了整个实验过程中脂质体疫苗的一致性。接种后12、14、16、18、20、22、24、26、28 d,肿瘤体积比较差异有统计学意义(P<0.05),小鼠体质量比较差异无统计学意义(P>0.05)。结论 甘露糖修饰的脂质体共同递送HPV16 E7多肽和佐剂CpG-ODN可增强小鼠抗晚期宫颈癌的活性,研究为不断优化治疗性HPV疫苗设计、增强治疗性HPV疫苗效力提供了重要基础,为宫颈癌的防治提供了新途径,也为开发有效靶向树突状细胞的新型疫苗提供了新思路。Objective To construct mannose-modified liposome co-delivering human papillomavirus(HPV) 16 E7 polypeptide and CpG oligodeoxynucleotides(ODN),evaluate the effect of the vaccine in local mouse model of advanced cervical cancer.Methods The research time was from March to November 2022.Twenty-four female C57BL/6 mice aged 6-8 weeks were selected to establish mouse cervical cancer model,mannose-modified liposome co-delivering HPV 16 E7 peptide and CpG-ODN were constructed,when the mouse model of locally advanced cervical cancer with a tumor volume of 200 mm~3,flow cytometry was used to detect the effect of vaccine on immune function of mice.Results Under transmission electron microscope,Lip E7/CpG was a spherical structure,after negative staining,the size of lipidosome changed from 60 nm to 120 nm,the diameter of lipidosome detected by dynamic light scattering was(122.21±8.37) nm.Lip E7/CpG was stable within 7 days when stored at(4±2) ℃,grain size and EE barely changed within 7 days,which ensured the consistency of liposome vaccine.At 12,14,16,18,20,22,24,26,and 28 days after inoculation,there was statistically significant difference in tumor volume(P<0.05),there was no statistically significant difference in weight of mice(P>0.05).Conclusion The co-delivery of HPV 16 E7 polypeptide and adjuvant CpG-ODN by mannose-modified liposomes can enhance the activity of mice against advanced cervical cancer,and the research results provide an important basis for continuously optimizing the design of therapeutic HPV vaccine and enhancing the efficacy of therapeutic HPV vaccine,providing a new way for prevention and treatment of cervical cancer,which also provide new ideas for development of new vaccines that effectively target DC.

关 键 词：甘露糖 脂质体 治疗性疫苗 宫颈癌 

分 类 号：R737.33[医药卫生—肿瘤]