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通过使用侵入性检测实现肿瘤靶向

Towards Tumor Targeting via Invasive Assay Using .

作者信息

Xavierselvan Marvin, Divecha Heena R, Hajra Mamta, Silwal Sushila, Macwan Isaac

机构信息

Department of Biomedical Engineering, Tufts University, Medford, MA, United States.

Department of Biomedical Engineering, University of Bridgeport, Bridgeport, CT, United States.

出版信息

Front Microbiol. 2021 Jul 22;12:697132. doi: 10.3389/fmicb.2021.697132. eCollection 2021.

DOI:10.3389/fmicb.2021.697132
PMID:34367097
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8341810/
Abstract

(AMB-1) are a species of magnetotactic bacteria (MTB) that are capable of orienting along the earth's magnetic field lines through their organelles called magnetosomes. Many studies have shown that certain engineered bacteria can infect the tumor cells, resulting in a controlled death of a tumor. This work deals with a technique utilizing AMB-1 along a predefined path through magnetotaxis, which can pave a way for selective doping as well as isolation of the tumor cells from a group of healthy cells through a magnetic invasive assay. For such a control, a tiny mesh of vertical electrical coils each having a diameter of ∼3 mm is fabricated, which establishes the path for the bacteria to move along the magnetic field lines. The molecular dynamics (MD) simulations at the interface of the bacterial cell surface proteins (MSP-1 and flagellin) and Chinese hamster ovary (CHO) cell surface containing cytoplasmic and extracellular proteins (BSG, B2M, SDC1, AIMP1, and FOS) are shown to establish an association between the AMB-1 and the host CHO cells. It is found that the CHO protein structure is compromised, which disables the activation of its defense function, allowing the bacteria to interact and survive. The experimental demonstration involves the CHO cells' interaction with the AMB-1 and isolation of selected CHO cells. It is found that AMB-1-integrated CHO cells successfully moved along the magnetic field lines generated by the coils. Statistical analysis performed for the assay showed that AMB-1 cells were found to be viable after co-incubating with CHO cells, and the number of viable cells post co-incubation over a period of 24 h showed a slight decrease in both cell population. Overall, 51% of AMB-1 cells and 67% of CHO cells were found viable 24 h post co-incubation. Scanning electron microscopy (SEM) along with energy-dispersive X-ray spectroscopy (EDAX) analysis revealed AMB-1/CHO cell morphology, the potential interaction between them, and the presence of magnetosomes with trace amounts of iron in the AMB-1-interacted CHO cells, confirming the successful AMB-1 integration.

摘要

嗜磁螺菌AMB-1是一种趋磁细菌,能够通过其称为磁小体的细胞器沿着地球磁场线定向。许多研究表明,某些工程细菌可以感染肿瘤细胞,导致肿瘤细胞可控死亡。这项工作涉及一种利用AMB-1通过趋磁作用沿着预定路径移动的技术,这可以为选择性掺杂以及通过磁侵入试验从一组健康细胞中分离肿瘤细胞铺平道路。为了实现这种控制,制作了一个由直径约3毫米的垂直电线圈组成的微小网格,该网格为细菌沿着磁场线移动建立了路径。分子动力学(MD)模拟显示,在细菌细胞表面蛋白(MSP-1和鞭毛蛋白)与含有细胞质和细胞外蛋白(BSG、B2M、SDC1、AIMP1和FOS)的中国仓鼠卵巢(CHO)细胞表面的界面处,AMB-1与宿主CHO细胞之间建立了关联。研究发现,CHO蛋白结构受到破坏,这使其防御功能无法激活,从而使细菌能够相互作用并存活。实验证明涉及CHO细胞与AMB-1的相互作用以及对选定CHO细胞的分离。研究发现,整合了AMB-1的CHO细胞成功地沿着线圈产生的磁场线移动。对该试验进行的统计分析表明,与CHO细胞共孵育后,发现AMB-1细胞是有活力 的,并且在24小时的共孵育期后,两个细胞群体中有活力的细胞数量均略有下降。总体而言,共孵育24小时后,发现51%的AMB-1细胞和67%的CHO细胞是有活力的。扫描电子显微镜(SEM)以及能量色散X射线光谱(EDAX)分析揭示了AMB-1/CHO细胞的形态、它们之间的潜在相互作用以及在与AMB-1相互作用的CHO细胞中存在含有微量铁的磁小体,证实了AMB-1的成功整合。

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