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选择一种新型CD19适配体用于将阿霉素靶向递送至淋巴瘤细胞。

Selection of a novel CD19 aptamer for targeted delivery of doxorubicin to lymphoma cells.

作者信息

Hu Yan, Li Xiaoou, An Yacong, Duan Jinhong, Yang Xian-Da

机构信息

Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.

出版信息

Oncotarget. 2018 Jun 1;9(42):26605-26615. doi: 10.18632/oncotarget.24902.

Abstract

CD19 is overexpressed in most human B cell malignancies and considered an important tumor marker for diagnosis and treatment. Aptamers are oligonucleotides that may potentially serve as tumor-homing ligand for targeted cancer therapy with excellent affinity and specificity. In this study, we selected a novel CD19 aptamer (LC1) that was a 59-nucleotide single strand DNA. The aptamer could bind to recombinant CD19 protein with a of 85.4 nM, and had minimal cross reactivity to bovine serum albumin (BSA) or ovalbumin (OVA). Moreover, the aptamer was found capable of binding with the CD19-positive lymphoma cells (Ramos and Raji), but not the CD19-negative cell lines (Jurkat and NB4). An aptamer-doxorubicin complex (Apt-Dox) was also formulated, and selectively delivered doxorubicin to CD19-positive lymphoma cells . The results indicate that aptamer LC1 can recognize CD19-positive tumor cells and may potentially function as a CD19-targeting ligand.

摘要

CD19在大多数人类B细胞恶性肿瘤中过度表达,被认为是诊断和治疗的重要肿瘤标志物。适体是寡核苷酸,可能作为肿瘤归巢配体用于靶向癌症治疗,具有优异的亲和力和特异性。在本研究中,我们筛选出一种新型CD19适体(LC1),它是一个59个核苷酸的单链DNA。该适体与重组CD19蛋白结合的解离常数为85.4 nM,与牛血清白蛋白(BSA)或卵清蛋白(OVA)的交叉反应最小。此外,发现该适体能够与CD19阳性淋巴瘤细胞(Ramos和Raji)结合,但不能与CD19阴性细胞系(Jurkat和NB4)结合。还制备了一种适体-阿霉素复合物(Apt-Dox),并将阿霉素选择性地递送至CD19阳性淋巴瘤细胞。结果表明,适体LC1可以识别CD19阳性肿瘤细胞,并可能作为CD19靶向配体发挥作用。

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