Abstract 3590: Targeted detection of ovarian cancer using functionalized iron oxide nanoparticles

Abstract

SuperParaMagnetic Relaxometry (SPMR) is a highly sensitive detection technology that can differentiate the magnetic signature of nanoparticles (NP) bound to tumor cells from unbound nanoparticles. Nanoparticles that reach and bind to the target cells are measurable by superconducting quantum interference device (SQUID) magnetometers (MRX instrument developed in house), while unbound nanoparticles such as those freely circulating in the bloodstream are not detected and bone and normal tissue do not produce any magnetic signal. We have developed a protocol to produce high precision 25nm+1nm (<7% dispersion) Fe3O4 nanoparticle core. These core nanoparticles are coated by a polymer shell functionalized with carboxylate groups. Antibody are then conjugated on the surface providing molecular targeting capabilities and PEG is also attached to the surface to reduce opsonization. In previous studies, we have demonstrated that when conjugated with anti-HER2 antibody such as Herceptin, these nanoparticles exhibited great specificity and selectivity towards HER2+ tumor cells in vitro and in vivo. In current studies, we expanded our nanoparticles applications to other type of cancers, such as ovarian cancer. The CA125 is a tissue-specific antigen expressed in ovarian cancer. It is associated with greater than 80% of epithelial ovarian neoplasms. OC125, a murine monoclonal antibody, reacts with glycosylation-dependent antigens present exclusively in the cleaved portion of the molecule. OC125 antibody is conjugated to our nanoparticles using the same strategy developed for Herceptin nanoparticles. Each nanoparticle contains one to three OC125 antibody molecules covalently attached to the surface based on ELISA analysis. Our results have shown that OC125-NP can distinguish CA125+ and CA125- cell lines, OVCAR3 and HeyA8 respectively. Positive signal can be competed out by pre-incubation with free OC125 antibody and negative cell line produce undetectable SPMR signal, demonstrating good sensitivity, specificity and selectivity. Antigen glypican-1 (GPC1) is a proteoglycan located on cell surface composed of a membrane-associated protein core anchored to the cytoplasmic membrane. GPC1 may play a functional role in the control of cell division and growth regulation. The expression of GPC1 has been found to be elevated in many cancer cells, including ovarian. Applying the same conjugation strategy developed for Herceptin NP, humanized anti-GPC1 antibody is conjugated to the nanoparticles with minor modification. GPC1-NP generate appreciable signal using SKOV3 cell line (GPC1+ ovarian cell lines) and the signal can be competed out by the presence of excess free GPC1 antibody. Together, these results suggest that in additional to breast cancer application, our antibody functionalized nanoparticle system can be developed for other targeted cancer detection, such as ovarian cancer. Citation Format: Marie Zhang, Eric Smith-Nguyen. Targeted detection of ovarian cancer using functionalized iron oxide nanoparticles. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3590.