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    Cancer Technologies

    (F-228) The Effects of Manganese Oxide Nanoparticle Concentrations on Magnetic Resonance Imaging (MRI) Signal Quenching in Breast Cancer Cells

    Saturday, October 14, 2023
    9:30 AM – 10:30 AM PDT
    Location: Exhibit Hall - Row F - Poster # 228
    Introduction:: Breast cancer is the most diagnosed cancer among women globally; throughout their lifetime, women have a 1 in 8 chance of developing the disease. Mammography is the most routinely used detection method for breast cancer screening; however, it can miss cancer present in women with dense breast tissue and can misdiagnose a benign mass as a malignant one. Magnetic resonance imaging (MRI) has superior soft tissue contrast to detect more breast cancers but still suffers from high false positive rates due to the conventional contrast agents used (e.g., gadolinium chelates). Gadolinium chelates provide constant bright MRI signal, will enter any well vascularized area to lead to high background, and lack the targeting needed to accurately distinguish benign and malignant tumors. Gadolinium chelates’ limitations have inspired us to develop a novel tumor targeted pH-sensitive MRI contrast agent consisting of manganese oxide (MnO), which only turns “ON” in acidic conditions such as the endosomes and lysosomes present inside cancer cells. The goal of this project was to assess how varied concentrations of Nano-Encapsulated Manganese Oxide (NEMO) particles affected the MRI signal inside benign versus malignant mammary cells.

    Materials and Methods:: NEMO particles were formulated through single emulsion of MnO nanocrystals with poly(lactic-co-glycolic) acid and poly(ethylene glycol); then, a tumor targeting peptide was attached to the surface of the particles via click chemistry. Three human mammary cell lines, MCF10A (benign control), T47D (luminal A breast cancer), and HCC1143 (triple negative breast cancer) were exposed for 1 hr to different concentrations of tumor-targeted NEMO particles ranging from 0 to 13 μg of Mn/mL. After exposure, cells were imaged with MRI to observe the dependency of the signal with increasing NEMO particle concentrations. Quenching, or the saturation of MRI signal, was assessed to determine the optimal concentration range for cancer detection. The mechanism behind the intracellular MRI signal changes was evaluated through determining the exact location of NEMO particles within cells (confocal), internalized total Mn content within labeled cells (ICP-MS) and the amount of released Mn2+ within cells that correlates to MRI signal (EPR).

    Results, Conclusions, and Discussions::


    In all cell lines, MRI signal was brighter as NEMO particle labeling concentration increased; however, the level of quenching was different between the benign control and breast cancer cells. MCF10A control cells experienced loss of MRI signal at lower NEMO particle concentrations with a peak at 1.63 μg Mn/mL, above which quenching occurred. T47D cells experienced a peak intensity at a higher labeling concentration of 6.5 μg Mn/mL, indicating that quenching effects may be stronger in benign cells. HCC1143 did not display a significant peak throughout any of the concentrations and stayed fairly stagnant throughout. ICP-MS data confirmed MRI signal quenching by demonstrating that higher NEMO particle labeling concentrations led to higher Mn internalization but not higher MRI signal. The reason behind the observed differences in MRI signal are currently being elucidated through assessing the kinetics of NEMO particle uptake and intracellular localization with confocal microscopy.





    Surprisingly, we observed that NEMO particles experienced differential levels of quenching in benign vs. malignant mammary cells as labeling concentrations were increased.     Further understanding of the contrast mechanism will help refine our nanoparticle design in future studies for optimized cancer detection. This will in turn allow for the opportunity to perform in vivo studies to determine MRI signal strength, specificity, toxicity and biodistribution over time in breast cancer bearing mice.



     



     


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