Targeting Mucin Protein Enables Rapid and Efficient Ovarian Cancer Cell Capture: Role of Nanoparticle Properties in Efficient Capture and Culture

Author:

Feely Nathan1,Wdowicz Anita1,Chevalier Anne2,Wang Ying2,Li Peng2,Rollo Fanny3,Lee Gil U.1ORCID

Affiliation:

1. Conway Institute for Biomedical Research and School of Chemistry University College Dublin 61 Adair, Sandymount Ave Dublin, CO. DUBLIN 00004 Ireland

2. Magnostics Ltd 2 Clifton Lane, Merrion Road Monkstown, Dublin A94 A306 Ireland

3. École nationale supérieure des ingénieurs en arts chimiques et technologiques Toulouse 31030 France

Abstract

AbstractThe development of specific and sensitive immunomagnetic cell separation nanotechnologies is central to enhancing the diagnostic relevance of circulating tumor cells (CTCs) and improving cancer patient outcomes. The limited number of specific biomarkers used to enrich a phenotypically diverse set of CTCs from liquid biopsies has limited CTC yields and purity. The ultra‐high molecular weight mucin, mucin16 (MUC16) is shown to physically shield key membrane proteins responsible for activating immune responses against ovarian cancer cells and may interfere with the binding of magnetic nanoparticles to popular immunomagnetic cell capture antigens. MUC16 is expressed in ≈90% of ovarian cancers and is almost universal in High Grade Serous Epithelial Ovarian Cancer. This work demonstrates that cell bound MUC16 is an effective target for rapid immunomagnetic extraction of expressor cells with near quantitative yield, high purity and viability from serum. The results provide a mechanistic insight into the effects of nanoparticle physical properties and immunomagnetic labeling on the efficiency of immunomagnetic cell isolation. The growth of these cells has also been studied after separation, demonstrating that nanoparticle size impacts cell‐particle behavior and growth rate. These results present the successful isolation of “masked” CTCs enabling new strategies for the detection of cancer recurrence and select and monitor chemotherapy.

Funder

Science Foundation Ireland

Publisher

Wiley

Subject

Biomaterials,Biotechnology,General Materials Science,General Chemistry

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