Varying Oleylamine: Dibenzyl Ether Ratio for Fine-Tuning Manganese Oxide Nanoparticle Diameter and Controlled Release

Jenna Vito*, Alexander Pueschel*, Celia Martinez de la Torre and Margaret Bennewitz, Department of Chemical and Biomedical Engineering, Benjamin M. Statler College of Engineering and Mineral Resources, West Virginia University, Morgantown, WV 26505

Field (Broad Category): Engineering (Physical Sciences & Engineering) 

Student’s Major: Chemical Engineering 

The ultimate goal of this research project is to develop a contrast agent to reduce false positive and false negative imaging results associated with current breast cancer diagnosis techniques. Gadolinium chelates are the current clinically approved contrast agents for breast magnetic resonance imaging (MRI), but they are always “on”, highlight any vascularized structure, and lack targeting allowing benign and malignant breast tumors to be enhanced. By utilizing targeted pHsensitive manganese oxide (MnO) nanoparticles, a contrast agent can be developed that only turns “on” 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+ thereby enhancing MRI signals. By changing the ratio of oleyl amine (OA) and dibenzyl ether (DE) involved in MnO nanoparticle synthesis between 60:0 and 10:50, we reduced the average size of the MnO nanoparticles with the 10:50 ratio creating the smallest diameter of 18 ±5.5 nm, while the 50:10 ratio created the largest diameter of 38.8±14.6nm. MnO nanoparticles were incubated at three 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). The only significant release of Mn2+ was obtained at pH 5 (~50% in 24hr), indicating the importance of targeting MnO nanoparticles inside of cancer cells. The smallest nanoparticles had a ~7% increase in Mn2+ release at low pH by 24 hours compared to the largest nanoparticles, indicating that size reduction increases free Mn2+ to enhance the MRI signal. 

Funding: 

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