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

Abstract

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 ≈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.

MUC1 and MUC16: critical for immune modulation in cancer therapeutics

“…Feely et al. developed immunomagnetic nanoparticles targeting MUC16, which efficiently extract circulating tumor cells (CTCs) in liquid biopsies, leveraging the widespread expression of MUC16 in high-grade serous ovarian cancer to provide an effective targeting technique for ovarian cancer detection ( 134 ).…”

The Impact of Surface Modifier on Magnetic Nanoparticle Properties and Their Application in CD3+T Cell Separation

“…Fe 3 O 4 nanoparticles are of paramount importance in the realm of nanobiology, offering nontoxic and biocompatible systems for a wide array of biomedical applications. These include serving as contrast agents for magnetic resonance imaging (MRI), − effectors in magnetic hyperthermia, magnetic carriers for targeted drug delivery, − and for magnetic activated cell separation (MACS). − Cell separation, a crucial technology in modern biotechnology, involves isolation of the desired phenotype of target cells from a heterogeneous cell population. In current biomedical treatments, numerous rare target cells are separated from whole blood or biological tissues for further diagnostic or therapeutic purposes.…”