白蛋白亲和肽-黑色素瘤抗原肽胶束淋巴结的靶向性研究
Study on targeting lymph nodes of the micelle from albumin binding domain and melanoma antigen peptide
作者:李琳;张志荣;龚涛;孙逊;
Author:
收稿日期: 年卷(期)页码:2018,33(01):-1-4
期刊名称:华西药学杂志
Journal Name:WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字:淋巴结靶向;白蛋白;白蛋白亲和肽;黑色素瘤抗原肽;自组装;胶束;亲和性;多肽;疫苗
Key words:
基金项目:国家自然科学基金资助项目(批准号:81690261、81673362)
中文摘要
目的制备环状白蛋白亲和肽-黑色素瘤抗原肽(cABD-Trp2)胶束,探究胶束与白蛋白的亲和力及其淋巴结的靶向性。方法具白蛋白亲和性的环状多肽序列与抗原肽共价连接后,在水溶液中自组装成cABD-Trp2胶束,利用透射电镜观察其形态和粒径;通过非变性聚丙烯酰胺凝胶电泳、荧光能量共振转移、生物膜层干涉技术来考察胶束与白蛋白间的亲和性;经荧光成像系统来考察cABD-Trp2胶束在体内对淋巴结的靶向性。结果成功制备了cABD-Trp2胶束,其形态为不规则的球形,粒径约25 nm。胶束形成后仍能与白蛋白亲和,与游离抗原或弗氏不完全佐剂载抗原比较,胶束能显著提高抗原对淋巴结的靶向性。结论白蛋白亲和多肽与抗原肽形成胶束后仍能与白蛋白有效亲和,通过内源性白蛋白,可使抗原有效传递到淋巴结,为疫苗设计提供了新思路。
参考文献
[1]Naik S,Bouladoux N,Linehan JL,et al.Commensal-dendriticcell interaction specifies a unique protective skin immune signature[J].Nature,2015,520(7545):104-108.
[2]Bachmann MF,Jennings GT.Vaccine delivery:A matter of size,geometry,kinetics and molecular patterns[J].Nature Rev Immunology,2010,10(11):787-796.
[3]Davies-Venn CA,Angermiller B,Wilganowski N,et al.Albuminbinding domain conjugate for near-infrared fluorescence lymphatic imaging[J].Mol Imag Bio,2012,14(3):301-314.
[4]Froehlich E,Mandeville JS,Jennings CJ,et al.Dendrimers bind human serum albumin[J].J Physic Chem B,2009,113(19):6986-6993.
[5]Liu H,Moynihan KD,Zheng Y,et al.Structure-based programming of lymph-node targeting in molecular vaccines[J].Nature,2014,507(7493):519-522.
[6]Dennis MS,Jin H,Dugger D,et al.Imaging tumors with an albumin-binding Fab,a novel tumor-targeting agent[J].Cancer Research,2007,67(1):254-261.
[7]Palucka K,Banchereau J.Cancer immunotherapy via dendritic cells[J].Nature Rev Cancer,2012,12(4):265.
[8]Den Haan JM,Lehar SM,Bevan MJ.CD8+but not CD8-dendritic cells cross-prime cytotoxic Tcells in vivo[J].Exp Med,2000,192:1685-1696.
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