Tuning the size and composition of manganese oxide nanoparticles through varying temperature ramp and aging time

摘要

Manganese oxide (MnO) nanoparticles (NPs) can serve as robust pH-sensitive contrast agents for magnetic resonance imaging (MRI) due to Mn 2+ release at low pH, which generates a ~30 fold change in T 1 relaxivity. Strategies to control NP size, composition, and Mn 2+ dissolution rates are essential to improve diagnostic performance of pH-responsive MnO NPs. We are the first to demonstrate that MnO NP size and composition can be tuned by the temperature ramping rate and aging time used during thermal decomposition of manganese(II) acetylacetonate. Two different temperature ramping rates (10°C/min and 20°C/min) were applied to reach 300°C and NPs were aged at that temperature for 5, 15, or 30 min. A faster ramping rate and shorter aging time produced the smallest NPs of ~23 nm. Shorter aging times created a mixture of MnO and Mn 3 O 4 NPs, whereas longer aging times formed MnO. Our results indicate that a 20°C/min ramp rate with an aging time of 30 min was the ideal temperature condition to form the smallest pure MnO NPs of ~32 nm. However, Mn 2+ dissolution rates at low pH were unaffected by synthesis conditions. Although Mn 2+ production was high at pH 5 mimicking endosomes inside cells, minimal Mn 2+ was released at pH 6.5 and 7.4, which mimic the tumor extracellular space and blood, respectively. To further elucidate the effects of NP composition and size on Mn 2+ release and MRI contrast, the ideal MnO NP formulation (~32 nm) was compared with smaller MnO and Mn 3 O 4 NPs. Small MnO NPs produced the highest amount of Mn 2+ at acidic pH with maximum T 1 MRI signal; Mn 3 O 4 NPs generated the lowest MRI signal. MnO NPs encapsulated within poly(lactide-co-glycolide) (PLGA) retained significantly higher Mn 2+ release and MRI signal compared to PLGA Mn 3 O 4 NPs. Therefore, MnO instead of Mn 3 O 4 should be targeted intracellularly to maximize MRI contrast.