实时监测T细胞活化的多功能纳米探针。

IF 4.2 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Nanomedicine : nanotechnology, biology, and medicine Pub Date : 2022-08-01 DOI:10.2139/ssrn.4094098
O. Betzer, Yue Gao, Astar Shamul, M. Motiei, T. Sadan, R. Yehuda, Ayelet Atkins, C. Cohen, Mingwu Shen, Xiangyang Shi, R. Popovtzer
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引用次数: 0

摘要

基因工程T细胞是癌症免疫治疗的一种强有力的新方式。然而,它们在实体肿瘤中的临床应用具有挑战性,并且缺乏关于细胞在体内功能的关键知识。在这里,我们制造了一个由树状大分子组成的纳米探针,结合钙传感器和金纳米颗粒,用于实体肿瘤内工程T细胞的双峰监测。T细胞被改造成表达黑色素瘤特异性T细胞受体,并装载纳米探针,在小鼠黑色素瘤异种移植物中进行纵向监测。纳米探针钙传感器的荧光成像显示,随着时间的推移,肿瘤内T细胞的活化增加,可达24 h。纳米探针的金纳米粒子的计算机断层成像显示了细胞在肿瘤内的分布模式。定量分析显示肿瘤内T细胞数量。因此,这种纳米探针揭示了基因工程T细胞在肿瘤内的持久性、穿透性和功能状态,可以推进基于T细胞的免疫治疗和促进下一代活细胞成像。
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Multifunctional nanoprobe for real-time in vivo monitoring of T cell activation.
Genetically engineered T cells are a powerful new modality for cancer immunotherapy. However, their clinical application for solid tumors is challenging, and crucial knowledge on cell functionality in vivo is lacking. Here, we fabricated a nanoprobe composed of dendrimers incorporating a calcium sensor and gold nanoparticles, for dual-modal monitoring of engineered T cells within a solid tumor. T cells engineered to express a melanoma-specific T-cell receptor and loaded with the nanoprobe were longitudinally monitored within melanoma xenografts in mice. Fluorescent imaging of the nanoprobe's calcium sensor revealed increased intra-tumoral activation of the T cells over time, up to 24 h. Computed tomography imaging of the nanoprobe's gold nanoparticles revealed the cells' intra-tumoral distribution pattern. Quantitative analysis revealed the intra-tumoral T cell quantities. Thus, this nanoprobe reveals intra-tumoral persistence, penetration and functional status of genetically engineered T cells, which can advance T cell-based immunotherapy and promote next-generation live cell imaging.
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来源期刊
CiteScore
11.10
自引率
0.00%
发文量
133
审稿时长
42 days
期刊介绍: The mission of Nanomedicine: Nanotechnology, Biology, and Medicine (Nanomedicine: NBM) is to promote the emerging interdisciplinary field of nanomedicine. Nanomedicine: NBM is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.
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