Margaret Bennewitz, West Virginia University

Development of uMUC-1 targeted NEMO particles with pH-activatable MRI signal for enhanced detection of breast cancer cells

Host: Hacer Karats Bristow

Chemical and Biomedical Engineering
West Virginia University

Misdiagnosis is prevalent in young, high-risk women with dense breasts receiving breast cancer screening, resulting in needless follow-up testing, anxiety and medical costs. Compared to mammography, magnetic resonance imaging (MRI) detects more breast cancers but still suffers from high false positive rates due to the conventional contrast agents used, e.g., gadolinium (Gd)-chelates. The poor performance of Gd-chelates results from their lack of targeting and constant MRI signal which highlights both benign and malignant tumors. We currently lack improved contrast agents for accurate breast cancer detection. Towards this goal, my laboratory has developed Nano-Encapsulated Manganese Oxide (NEMO) particles as a new pH-sensitive tumor specific MRI contrast agent. We have shown that NEMO particles localize to breast cancer cells through their peptide targeting to underglycosylated mucin-1 (uMUC-1), overexpressed in cancer. Once internalized by cancer cells, NEMO particles dissolve in acidic endosomes and lysosomes, producing a robust pH-activated MRI signal in ~30 minutes. Our in vivo preliminary data in mouse models demonstrates that NEMO particles are safely tolerated after multiple injections and are rapidly eliminated from systemic organs in 24 hours. In vivo, NEMO particles detect breast cancer with higher specificity and equivalent contrast to Gd-chelates. Our team is also pioneering microfluidic MRI of organ-on-a-chip models for high throughput in vitro contrast testing under dynamic flow. We have shown proof-of-concept for tracking NEMO particle uptake in microfluidic chips using confocal microscopy and MRI. NEMO particles are expected to reduce the misdiagnosis of breast MRI and are applicable to other tumor types.