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

The 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 approximate to 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.

Automated summary

The development of specific and sensitive immunomagnetic cell separation nanotechnologies is crucial for improving cancer patient outcomes. The use of limited biomarkers for enriching circulating tumor cells (CTCs) has resulted in low CTC yields and purity. This study demonstrates that cell bound MUC16 can be effectively targeted for rapid immunomagnetic extraction of CTCs with high yield, purity, and viability. The results also provide insights into the impact of nanoparticle physical properties on the efficiency of immunomagnetic cell isolation.