Tracking the expression of therapeutic protein targets in rare cells via antibody-mediated nanoparticle labelling and sorting

• Published in: Nature biomedical engineering Vol. 5; no. 1; pp. 41 - 52
• Main Authors: Labib, Mahmoud, Wang, Zongjie, Ahmed, Sharif U., Mohamadi, Reza M., Duong, Bill, Green, Brenda, Sargent, Edward H., Kelley, Shana O.
• Format: Journal Article
• Language: English
• Published: 27-07-2020
• ISSN: 2157-846X
• DOI: 10.1038/s41551-020-0590-1

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.