(31g) Tuning the Size and Composition of Manganese Oxide Nanoparticles for Magnetic Resonance Imaging of Breast Cancer

Magnetic resonance imaging (MRI) can detect more breast cancers than mammography, the current gold standard screening technique. However, MRI still produces a high false positive rate of up to 25% due to the commonly used gadolinium contrast agent, which is always active and nonspecifically highlights all vascularized tissue in the body. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing manganese oxide (MnO) cores have been introduced as novel pH-sensitive contrast agents and can be activated upon tumor cell uptake into low pH endosomes to provide selective MRI contrast at the cancer site through Mn²⁺ generation. The objective of this study was to enhance MRI contrast by reducing MnO core size. Smaller MnO cores should allow for maximum packing volume into PLGA nanoparticles and faster controlled release of Mn²⁺ through a greater surface area to volume ratio. MnO cores were fabricated through thermal decomposition of manganese (II) acetylacetonate using two different temperature ramps (10^oC/min and 20^oC/min) and aged at 300^oC for increasing time periods of 5, 15, and 30 minutes. This study is the first to show that temperature ramping rate and aging time impact both the resulting size and chemistry of MnO cores. Synthesized MnO cores were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), and Mn²⁺ controlled release at pH 5 (to mimic endosomal pH inside cells), 6.5 (to mimic the tumor extracellular space), and 7.4 (to mimic the blood). A faster temperature ramp and shorter aging time at 300^oC reduced MnO core size to 23.4 nm ± 11.7 nm as shown by TEM. XRD spectra revealed that pure MnO was obtained with longer overall reaction times; however, shorter overall reaction times produced a mixture of MnO and Mn₃O₄. Compared to MnO, Mn₃O₄ is expected to have slower Mn²⁺ production rates. Surprisingly, all synthesized cores had ~46% dissociation to Mn²⁺ over 24 hours in pH 5 media mimicking endosomes. Minimal Mn²⁺ release was found at pH 6.5 and 7.4, indicating that MnO nanoparticles must be targeted intracellularly to obtain sufficient MRI contrast for breast cancer detection. Future studies will investigate the impact of changing the ratio of chemical reactants to achieve further MnO size reduction and decreased polydispersity, as well as develop surface targeting methods to enhance MnO nanoparticle endocytosis within human breast cancer cells.