Capturing and releasing of hepatocellular carcinoma EpCAM+ and EpCAM- circulating tumor cells based on photosensitive intelligent nanoreactor

IF 4.3 3区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Frontiers in Bioengineering and Biotechnology Pub Date : 2024-08-30 DOI:10.3389/fbioe.2024.1443843

Zhifang Mao, Meng Hu, Qinglin Shen

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Abstract

Epithelial cell adhesion molecule negative circulating tumor cells (EpCAM- CTCs) and EpCAM positive CTCs (EpCAM + CTCs) have different biological characteristics. Therefore, the isolation of EpCAM + CTCs and EpCAM- CTCs is a new strategy to study the heterogeneity of tumor cells. The azobenzene group (Azo) and cyclodextrin (CD) composite system forms a photosensitive molecular switch based on the effect of external light stimulation. We used the technology of specifically capturing CTCs using anti-EpCAM and aptamers functionalized nanochips. Both anti-EpCAM and aptamers can be connected to Azo through the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) modification process. Therefore, we assume that a photosensitive intelligent nanoreactor (PSINR) modified with anti-EpCAM can be used to capture EpCAM + CTCs; Utilizing the characteristics of aptamer and ligand binding, a PSINR modified with aptamer is used to capture EpCAM- CTCs; Then, two PSINRs were separated and stimulated with light to release EpCAM + CTCs and EpCAM- CTCs, respectively. Based on the isolation the EpCAM + CTCs and EpCAM- CTCs, we expected to reveal the key biological mechanisms of tumor recurrence, metastasis and drug resistance, and make the individualized treatment of liver cancer more targeted, safe and effective, and provide a new basis for the final realization of accurate and individualized treatment of tumors.

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基于光敏智能纳米反应器的肝癌 EpCAM+ 和 EpCAM- 循环肿瘤细胞的捕获和释放技术

上皮细胞粘附分子阴性的循环肿瘤细胞（EpCAM- CTCs）和EpCAM阳性的循环肿瘤细胞（EpCAM + CTCs）具有不同的生物学特性。因此，分离 EpCAM + CTCs 和 EpCAM- CTCs 是研究肿瘤细胞异质性的一种新策略。偶氮苯（Azo）基团和环糊精（CD）复合体系在外部光刺激作用下形成光敏分子开关。我们采用了抗 EpCAM 和适配体功能化纳米芯片特异性捕获 CTC 的技术。抗 EpCAM 和适配体都可以通过 1-乙基-3-（3-二甲基氨基丙基）碳二亚胺/N-羟基琥珀酰亚胺（EDC/NHS）修饰工艺与偶氮连接。因此，我们假定用抗 EpCAM 修饰的光敏智能纳米反应器（PSINR）可以捕获 EpCAM + CTCs；利用适配体和配体结合的特性，用适配体修饰的 PSINR 捕获 EpCAM- CTCs；然后将两个 PSINR 分离，用光刺激分别释放 EpCAM + CTCs 和 EpCAM- CTCs。在分离EpCAM + CTCs和EpCAM- CTCs的基础上，我们有望揭示肿瘤复发、转移和耐药的关键生物学机制，使肝癌的个体化治疗更具针对性、安全性和有效性，为最终实现肿瘤的精准个体化治疗提供新的依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Bioengineering and Biotechnology Chemical Engineering-Bioengineering

CiteScore

8.30

自引率

5.30%

发文量

2270

审稿时长

12 weeks

期刊介绍： The translation of new discoveries in medicine to clinical routine has never been easy. During the second half of the last century, thanks to the progress in chemistry, biochemistry and pharmacology, we have seen the development and the application of a large number of drugs and devices aimed at the treatment of symptoms, blocking unwanted pathways and, in the case of infectious diseases, fighting the micro-organisms responsible. However, we are facing, today, a dramatic change in the therapeutic approach to pathologies and diseases. Indeed, the challenge of the present and the next decade is to fully restore the physiological status of the diseased organism and to completely regenerate tissue and organs when they are so seriously affected that treatments cannot be limited to the repression of symptoms or to the repair of damage. This is being made possible thanks to the major developments made in basic cell and molecular biology, including stem cell science, growth factor delivery, gene isolation and transfection, the advances in bioengineering and nanotechnology, including development of new biomaterials, biofabrication technologies and use of bioreactors, and the big improvements in diagnostic tools and imaging of cells, tissues and organs. In today`s world, an enhancement of communication between multidisciplinary experts, together with the promotion of joint projects and close collaborations among scientists, engineers, industry people, regulatory agencies and physicians are absolute requirements for the success of any attempt to develop and clinically apply a new biological therapy or an innovative device involving the collective use of biomaterials, cells and/or bioactive molecules. “Frontiers in Bioengineering and Biotechnology” aspires to be a forum for all people involved in the process by bridging the gap too often existing between a discovery in the basic sciences and its clinical application.

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