(22f) Varying Oleylamine to Dibenzyl Ether Ratio for Fine-Tuning Manganese Oxide Nanoparticle Diameter and MRI Signal Intensity
AIChE Annual Meeting
2020
2020 Virtual AIChE Annual Meeting
Nanoscale Science and Engineering Forum
Nanobiotechnology for Sensors and Imaging
Monday, November 16, 2020 - 9:15am to 9:30am
The ultimate goal of this research project is to develop a contrast agent to reduce the number of false positive and false negative imaging results associated with current breast cancer diagnostic imaging techniques. Gadolinium chelates are the current clinically approved contrast agents for breast magnetic resonance imaging (MRI), but they are always âonâ and highlight any vascularized structure. Due to their lack of targeting, both benign and malignant breast tumors are enhanced with gadolinium. By utilizing tumor-targeted pH-sensitive manganese oxide (MnO) nanoparticles, a contrast agent can be developed that will only turn âonâ in the presence of the lower pH of endosomes/lysosomes inside cancer cells. Reducing the size of MnO nanoparticles should increase dissolution of MnO to Mn2+ at low pH to enhance MRI signal. MnO nanoparticles were synthesized through thermal decomposition of Mn(II) acetylacetonate in dibenzyl ether (DE) and oleylamine (OA) at a peak reaction temperature of 280oC for 30 minutes. The following ratios of OA:DE were used: 60:0, 50:10, 40:20, 30:30, 20:40, and 10:50 to investigate the effects of reactant conditions on nanoparticle size, Mn2+ release and MRI signal. MnO nanoparticles were characterized physically and chemically using transmission electron microscopy (TEM), x-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR). According to TEM, the 10:50 ratio created the smallest nanoparticle diameter of 19 ± 6 nm, while the 50:10 ratio created the largest nanoparticle diameter of 39 ± 15 nm. All nanoparticles were comprised of MnO (XRD) coated with oleylamine (FTIR). To further elucidate the effect of nanoparticle size and composition on the release of Mn2+ and resulting MRI signal, the smallest MnO nanoparticles (19 nm) were compared with MnO nanoparticles of a larger diameter (32 nm) and Mn3O4 nanoparticles of similar diameter (17 nm). Nanoparticles were incubated at 3 different pHs to measure Mn2+ release over time including pH 7.4 (blood pH), 6.5 (pH of tumor extracellular space), and 5 (endosome/lysosome pH) using inductively coupled plasma-optical emission spectroscopy (ICP-OES) and 1T MRI. The smallest MnO nanoparticles were the most efficient MRI contrast agents by releasing the highest amount of Mn2+ at pH 5 (~50% at 24 hr) and 6.5 (~11% at 24 hr), which produced the lowest T1 value (646 ms at 24 hr, pH 5) and maximum MRI signal at 1T; Mn3O4 nanoparticles generated the lowest MRI signal. Therefore, MnO nanoparticles instead of Mn3O4 should be utilized, and the nanoparticles should be targeted intracellularly to maximize MRI contrast generation. Future work includes fabricating hydrophilic MnO nanoparticles using phospholipid encapsulation and adding breast cancer-targeting peptides to enable specific detection of malignant versus benign breast tumors.