In Vivo MR Imaging of Glioma Recruitment of Adoptive T-Cells Labeled with NaGdF4-TAT Nanoprobes
In Vivo MR Imaging of Glioma Recruitment of Adoptive T-Cells Labeled with NaGdF4-TAT Nanoprobes
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神经胶质瘤招募用 NaGdF4-TAT 纳米探针标记的过继 T 细胞的体内 MR 成像
DOI：
10.1002/smll.201702951
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发表时间：
2018-01-18
期刊：
影响因子：
13.3
通讯作者：
Yao, Zhenwei
中科院分区：
文献类型：
--
作者：
Zhang, Hua;Wu, Yue;Yao, Zhenwei
免疫治疗是治疗胶质瘤术后残留病灶的最有前途的方法之一。然而，过继转移的T细胞在体内的命运尚不清楚，阻碍了对这种新兴疗法的理解。因此，非常需要开发这些T细胞到胶质瘤的非侵入性和定量体内跟踪，以更好地鉴定迁移命运，并提供靶向胶质瘤的过继性T细胞免疫疗法的结果的客观评价。在这项工作中，超小的T-1 MR为基础的纳米探针，NaGdF 4-达特，作为分子探针具有高纵向弛豫（8.93 mm（-1）s（-1））的设计。通过HIV-1反式激活因子（达特）肽，近95%的过继性T细胞被NaGdF 4-达特纳米探针标记，而对标记的T细胞没有任何可测量的副作用，这在标记功效方面显著上级对照异硫氰酸荧光素-NaGdF 4。在静脉输注10（7）个标记的T细胞后24小时，标记的过继性T细胞簇可通过T-1加权MR成像在原位GL 261-胶质瘤模型中灵敏地追踪。体外和体内实验均表明，NaGdF 4-达特纳米探针标记T细胞可能是一种有前途的跟踪过继性T细胞的方法，以提高我们对胶质瘤过继性免疫治疗中病理生理学的理解。
Adoptive T lymphocyte immunotherapy is one of the most promising methods to treat residual lesions after glioma surgery. However, the fate of the adoptively transferred T-cells in vivo is unclear, hampering the understanding of this emerging therapy. Thus, it is highly desirable to develop noninvasive and quantitative in vivo tracking of these T-cells to glioma for better identification of the migratory fate and to provide objective evaluation of outcomes of adoptive T-cell immunotherapy targeting glioma. In this work, ultrasmall T-1 MR-based nanoprobes, NaGdF4-TAT, as molecular probes with high longitudinal relaxivity (8.93 mm(-1) s(-1)) are designed. By means of HIV-1 transactivator (TAT) peptides, nearly 95% of the adoptive T-cells are labeled with the NaGdF4-TAT nanoprobes without any measurable side effects on the labeled T-cells, which is remarkably superior to that of the control fluorescein isothiocyanate-NaGdF4 concerning labeling efficacy. Labeled adoptive T-cell clusters can be sensitively tracked in an orthotopic GL261-glioma model 24 h after intravenous infusion of 10(7) labeled T-cells by T-1-weighted MR imaging. Both in vitro and in vivo experiments show that the NaGdF4-TAT nanoprobes labeling of T-cells may be a promising method to track adoptive T-cells to improve our understanding of the pathophysiology in adoptive immunotherapy for gliomas.