Tracking the expression of therapeutic protein targets in rare cells by antibody-mediated nanoparticle labelling and magnetic sorting
| Autor: | Bill Duong, Mahmoud Labib, Reza M. Mohamadi, Shana O. Kelley, Brenda J. Green, Zongjie Wang, Sharif Uddin Ahmed, Edward H. Sargent |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Cytological Techniques Biomedical Engineering Medicine (miscellaneous) Nanoparticle Mice Nude Bioengineering Mitochondrion Article 03 medical and health sciences Prostate cancer Mice 0302 clinical medicine Prostate Labelling medicine Biomarkers Tumor Animals Humans Magnetite Nanoparticles biology Chemistry Antibodies Monoclonal Prostatic Neoplasms Proteins medicine.disease Neoplastic Cells Circulating Computer Science Applications 030104 developmental biology medicine.anatomical_structure Cytoplasm biology.protein Cancer research Female Antibody Nucleus 030217 neurology & neurosurgery Biotechnology |
| Zdroj: | Nat Biomed Eng |
| ISSN: | 2157-846X |
| Popis: | Molecular-level features of tumours can be tracked via single-cell analyses of circulating tumour cells (CTCs). Yet single-cell measurements of protein expression for rare CTCs are hampered by the presence of a large number of non-target cells. Here, we show that the antibody-mediated labelling of intracellular proteins in the nucleus, mitochondria, and cytoplasm of human cells with magnetic nanoparticles enables the analysis of target proteins at the single-cell level by sorting the cells according to their nanoparticle content in a microfluidic device with cell-capture zones sandwiched between arrays of magnets. We used the magnetic labelling and cell-sorting approach to track the expression of therapeutic protein targets in CTCs isolated from blood samples of mice with orthotopic prostate xenografts and from patients with metastatic castration-resistant prostate cancer. We also show that mutated proteins that are drug targets or markers of therapeutic response can be directly identified in CTCs and analysed at the single-cell level, and used to predict how mice with drug-susceptible and drug-resistant pancreatic tumour xenografts respond to therapy. |
| Databáze: | OpenAIRE |
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