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用于CAR-T细胞功能验证及肿瘤细胞/组织检测的双光子荧光聚多巴胺纳米点

Two-photon fluorescent polydopamine nanodots for CAR-T cell function verification and tumor cell/tissue detection.

作者信息

Ma Baojin, Liu Feng, Zhang Shan, Duan Jiazhi, Kong Ying, Li Zhao, Tang Dongqi, Wang Wenjuan, Ge Shaohua, Tang Wei, Liu Hong

机构信息

State Key Laboratory of Crystal Materials, Shandong University, Jinan, Shandong 250100, China.

出版信息

J Mater Chem B. 2018 Oct 28;6(40):6459-6467. doi: 10.1039/c8tb01930d. Epub 2018 Sep 19.

Abstract

Chimeric antigen receptor T-Cell (CAR-T) immunotherapy has been regarded as one of the most promising methods for cancer therapy. How to verify CAR-T cell function and efficiency is very significant for clinical applications. Meanwhile, the identification of tumor cells/tissues is very important for tumor diagnosis and operation. In this study, biocompatible and mass-produced polydopamine (PDA) nanodots have been prepared by a facile method. Oxidized polydopamine (OPDA) can be synthesized by the reaction between PDA and hydrogen peroxide at atmospheric pressure and temperature, and it possesses both one-photon and two-photon fluorescence properties. OPDA nanodots can image living cells for long time periods without mitosis and proliferation inhibition. After ingestion of OPDA nanodots, Raji cells can be used to verify CAR-T cell lethality and efficiency by visualization through fluorescence. The fluorescence intensity change originating from the conversion of PDA into OPDA can function as a signal to identify the tumor and normal cells/tissues because of the different concentration of ROS in tumor cells (high) and normal cells (low). Therefore, the facile synthesis of mass-produced novel organic nanodots with two-photon fluorescence properties will have wide applications in long time living cell imaging without mitosis and proliferation inhibition, CAR-T cell function verification and tumor cell/tissue detection.

摘要

嵌合抗原受体T细胞(CAR-T)免疫疗法被视为癌症治疗最具前景的方法之一。如何验证CAR-T细胞的功能和效率对临床应用而言至关重要。同时,肿瘤细胞/组织的识别对肿瘤诊断和手术非常重要。在本研究中,已通过一种简便方法制备了具有生物相容性且可大规模生产的聚多巴胺(PDA)纳米点。氧化聚多巴胺(OPDA)可通过PDA与过氧化氢在常压和常温下反应合成,它具有单光子和双光子荧光特性。OPDA纳米点能够长时间对活细胞成像,且不会抑制有丝分裂和增殖。摄入OPDA纳米点后,Raji细胞可用于通过荧光可视化来验证CAR-T细胞的杀伤力和效率。由于肿瘤细胞(高)和正常细胞(低)中活性氧浓度不同,PDA转化为OPDA所引起的荧光强度变化可作为识别肿瘤和正常细胞/组织的信号。因此,简便合成具有双光子荧光特性的大规模新型有机纳米点将在长时间活细胞成像(无有丝分裂和增殖抑制)、CAR-T细胞功能验证及肿瘤细胞/组织检测方面有广泛应用。

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