Encapsulation of Manganese Oxide Nanoparticles to Maximize MRI Signal Intensity

Mara Looney-Sanders*, Celia Martinez de la Torre, Margaret Bennewitz, Ph.D.
Benjamin M. Statler College of Engineering and Mineral Resources, West Virginia University, Morgantown, WV 26506

Presentation Category: Physical Sciences & Engineering (Poster presentation)

Student’s Major: Engineering

Breast cancer is one of the most common cancers affecting women worldwide. To detect breast cancer early, magnetic resonance imaging (MRI) currently uses gadolinium (Gd) chelates as the main contrast agent. However, Gd chelates do not differentiate between malignant and benign tumors, which leads to false positives (misdiagnosed benign breast tumors), and cancer may be missed (false negatives). Manganese oxide (MnO) nanoparticles (NPs) have superior MRI signals and show potential in targeting malignant tumors using pH sensitivity, where the contrast will turn “ON” after internalization by the cancer cells. The ultimate goal of our research is to develop a contrast agent to reduce false positive and false negative imaging results associated with current breast MRI. Two methods were tested to make the MnO NPs hydrophilic: 1) MnO NPs were encapsulated with poly(lactic-co-glycolic) acid (PLGA) polymer using an oil-in-water emulsion procedure or 2) MnO NPs were coated with phospholipid micelles. Based on transmission electron microscopy (TEM), dynamic light scattering (DLS), and Fourier transform infrared spectroscopy (FTIR), PLGA encapsulation resulted in smaller NP diameters. As smaller particles have a higher surface-area-to-volume ratio, they were expected to dissolve faster in low pH conditions. PLGA MnO NPs were incubated at three pHs over 24 hr including pH 7.4 (blood pH), 6.5 (pH of tumor extracellular space), and 5 (endosome/lysosome pH). Significant MRI contrast and reduced T1 values were only observed at pH 5, meaning that PLGA MnO NPs need to be targeted inside cancer cells to create a robust bright signal.

Funding: Federal Work Study, WVU Department of Chemical and Biomedical Engineering

Program/mechanism supporting research/creative efforts: WVU's Research Apprenticeship Program (RAP) & accompanying HONR 297-level course