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利用生物标志物和磁性粒子光谱技术对胰腺癌循环肿瘤细胞进行高级检测。

Advanced Detection of Pancreatic Cancer Circulating Tumor Cells Using Biomarkers and Magnetic Particle Spectroscopy.

作者信息

Dinari Ali, Ahmad Hafiz Ashfaq, Oh Seungjun, Kim Yun-Hee, Yoon Jungwon

机构信息

Department of AI Convergence, Gwangju Institute of Science and Technology, Gwangju, 61005, Republic of Korea.

Department of Medical Physics, M. Smoluchowski Institute of Physics, Jagiellonian University, ul. S. Łojasiewicza 11, 30-348, Krakow, Poland.

出版信息

Nanotheranostics. 2025 Jun 12;9(2):171-185. doi: 10.7150/ntno.110074. eCollection 2025.


DOI:10.7150/ntno.110074
PMID:40568369
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12188535/
Abstract

Pancreatic ductal adenocarcinoma (PDAC) typically develops without symptoms, and its aggressive progression combined with late-stage diagnosis underscores the critical need for improved early detection strategies. Circulating tumor cells (CTCs) in blood are potential biomarkers for PDAC. In this study, the detection of pancreatic cancer-associated CTCs was evaluated using two magnetic-based diagnostic systems in a comparative approach. Two distinct nanotheranostic platforms were developed: monoclonal antibody-conjugated magnetic nanoparticles (mAbs-MNPs) and magnetized exosomes (termed Magxosomes). Anti-mesothelin and anti-vimentin were used as monoclonal antibodies, while mesenchymal stem cells (MSCs) treated with MNPs served as the source of Magxosomes. Characterization of nano-systems was performed using dynamic light scattering (DLS), inductively coupled plasma mass spectrometry (ICP-MS), nanoparticle tracking analysis (NTA), and transmission electron microscopy (TEM). Blood samples were collected from pancreatic cancer mouse models, treated with nanotheranostic platforms, and analyzed using a homemade magnetic particle spectroscopy (MPS) device. The detection of pancreatic cancer-associated CTCs was investigated using nanotheranostic platforms alongside an MPS instrument. In this context, the mAbs-MNPs systems demonstrated varying efficiencies in the diagnosis of CTCs, with Ant-V-MNPs (anti-vimentin conjugated MNPs) achieving 27.47%, Ant-M-MNPs (anti-mesothelin conjugated MNPs) at 13.59%, and a 50:50 mixture of Ant-M-MNPs: Ant-V-MNPs showing an efficiency of 19.73%. Conversely, the efficiencies of Magxosomes were notably higher. Bone marrow stem cell (BMSC)-derived Magxosomes achieved an average efficiency of 63.39%, while adipose-derived stem cell (ADSC)-derived Magxosomes exhibited an average efficiency of 56.23%. This study introduces a promising method for early pancreatic cancer diagnosis by detecting CTCs in blood. It employs a non-invasive, rapid test using an advanced MPS instrument (1 ng detection limit) and nanotheranostic platforms. Results confirm the system's robustness in identifying pancreatic cancer CTCs. This approach may support future developments in cancer diagnostics and monitoring.

摘要

胰腺导管腺癌(PDAC)通常在无症状的情况下发展,其侵袭性进展加上晚期诊断突出了改进早期检测策略的迫切需求。血液中的循环肿瘤细胞(CTC)是PDAC的潜在生物标志物。在本研究中,使用两种基于磁性的诊断系统以比较的方法评估胰腺癌相关CTC的检测。开发了两种不同的纳米诊疗平台:单克隆抗体偶联磁性纳米颗粒(mAbs-MNPs)和磁化外泌体(称为磁小体)。抗间皮素和抗波形蛋白用作单克隆抗体,而用MNPs处理的间充质干细胞(MSC)作为磁小体的来源。使用动态光散射(DLS)、电感耦合等离子体质谱(ICP-MS)、纳米颗粒跟踪分析(NTA)和透射电子显微镜(TEM)对纳米系统进行表征。从胰腺癌小鼠模型中采集血样,用纳米诊疗平台处理,并使用自制的磁性颗粒光谱(MPS)装置进行分析。使用纳米诊疗平台和MPS仪器研究胰腺癌相关CTC的检测。在这种情况下,mAbs-MNPs系统在CTC诊断中表现出不同的效率,抗波形蛋白偶联MNPs(Ant-V-MNPs)达到27.47%,抗间皮素偶联MNPs(Ant-M-MNPs)为13.59%,Ant-M-MNPs与Ant-V-MNPs 50:50的混合物显示效率为19.73%。相反,磁小体的效率明显更高。骨髓干细胞(BMSC)来源的磁小体平均效率达到63.39%,而脂肪来源干细胞(ADSC)来源的磁小体平均效率为56.23%。本研究通过检测血液中的CTC引入了一种有前景的早期胰腺癌诊断方法。它采用使用先进的MPS仪器(检测限为1 ng)和纳米诊疗平台的非侵入性快速检测。结果证实了该系统在识别胰腺癌CTC方面的稳健性。这种方法可能支持癌症诊断和监测的未来发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c8b/12188535/ef6ea928d21e/ntnov09p0171g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c8b/12188535/ef6ea928d21e/ntnov09p0171g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c8b/12188535/ab3f55c201c4/ntnov09p0171g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c8b/12188535/8e4b44f01f8f/ntnov09p0171g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c8b/12188535/b9df9a0d0492/ntnov09p0171g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c8b/12188535/cb89e1e4b177/ntnov09p0171g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c8b/12188535/0c24c6f914de/ntnov09p0171g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c8b/12188535/ef6ea928d21e/ntnov09p0171g006.jpg

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本文引用的文献

[1]
Greatly isolated heterogeneous circulating tumor cells using hybrid engineered cell membrane-camouflaged magnetic nanoparticles.

J Nanobiotechnology. 2024-5-8

[2]
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Biology (Basel). 2023-5-12

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Int J Mol Sci. 2023-2-10

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J Phys Chem C Nanomater Interfaces. 2021-8-12

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Sensors (Basel). 2022-9-4

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Formation of Visible Aggregates between Rolling Circle Amplification Products and Magnetic Nanoparticles as a Strategy for Point-of-Care Diagnostics.

ACS Omega. 2021-11-23

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Signal Transduct Target Ther. 2021-11-22

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Nano Converg. 2021-8-16

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