Caveat Emptor: Commercialized Manganese Oxide Nanoparticles Exhibit Unintended Properties

Nano-encapsulated manganese oxide (NEMO) particles are noteworthy contrast agents for magnetic resonance imaging (MRI) due to their bright, pH-switchable signal ("OFF" to "ON" at low pH), high metal loading, and targeting capability for increased specificity. For the first time, we performed a head-to-head comparison of NEMO particles from In-house and commercialized sources (US Nano vs Nanoshel) to assess their potential as bright T1 MRI contrast agents. Manganese oxide nanocrystals (MnO, Mn2O3, and Mn3O4) were systematically evaluated for size, chemistry, release of manganese ions, and MRI signal pre- and post-encapsulation within poly(lactic-co-glycolic acid) (PLGA). Suprisingly, a majority of the commercialized formulations were not as advertised by displaying unintended sizes, morphologies, chemistry, dissolution profiles, and/or MRI signal that precludes in vivo use. US Nano's Mn3O4 and Mn2O3 nanocrystals contained impurities that impacted Mn ion release as well as micron-sized rodlike structures. Nanoshel's MnO and Mn2O3 nanoparticles had very large hydrodynamic sizes (>600 nm). In-house MnO and Nanoshel's Mn3O4 nanoparticles demonstrated the best characteristics with brighter T1 MRI signals, small hydrodynamic sizes, and high encapsulation efficiencies. Our findings highlight that researchers must confirm the properties of purchased nanomaterials before utilizing them in desired applications, as their experimental success may be impacted.