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

Abstract

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.

PEGylation of Metal Oxide Nanoparticles Modulates Neutrophil Extracellular Trap Formation

“…NP synthesis and polymer encapsulation were performed under a chemical fume hood. According to established methods, MnO and Fe 3 O 4 NPs were fabricated via thermal decomposition of Mn(AcAc) 2 , or Fe(AcAc) 3 , respectively [ 19 , 86 , 87 ]. Briefly, for thermal decomposition, 6 mmol of Mn(AcAc) 2 for MnO and 3 mmol of Fe(AcAc) 3 for Fe 3 O 4 was dissolved in 10 mL of oleylamine and 50 mL of dibenzyl ether.…”

“…Using a previously established oil-in-water emulsion technique [ 19 ], the metal oxide NPs were encapsulated in PLGA with either 0%, 2.5%, or 5% ( w / w ) PLGA–PEG co-block polymer with dichloromethane (DCM) as the organic solvent and PVA as the stabilizing agent [ 19 , 88 ]. A 1:2 ratio ( w / w ) of metal oxide to polymer was added to the DCM.…”

“…Bare metal oxide NP samples were prepared for transmission electron microscopy (TEM), high-resolution TEM (HRTEM), and selected area electron diffraction (SAED) according to previous studies [ 19 , 86 ] and were imaged using a JEOL JEM-2100 transmission electron microscope at 200 kV. The dry-size diameters and d-parameters for the bare metal oxide NPs were obtained using ImageJ software.…”

“…Due to these concerns and the favorable magnetic properties of metal oxides, metal oxide NPs have emerged as attractive possible alternatives to traditional GBCAs. Iron oxide (Fe 2 O 3 or Fe 3 O 4 ) and manganese oxide (MnO, MnO 2 , or Mn 3 O 4 ) are two such NP formulations, with iron oxide providing T 2 or T 2 *-weighted contrast and manganese oxide providing T 1 -weighted contrast [ 19 ].…”

“…A key advantage of NPs lies in their customizability; different physicochemical properties of NPs can be altered to achieve the desired goal including size [ 20 , 21 , 22 , 23 , 24 ], shape [ 25 , 26 , 27 ], charge [ 24 , 28 , 29 ], type of contrast agent [ 19 , 30 , 31 ], polymer or lipid encapsulation [ 19 , 31 , 32 , 33 , 34 ], surface attachments (e.g., stealth polymers) [ 35 ], and the presence of targeting agents [ 36 , 37 ]. However, each modification alters how a given NP formulation will interact with blood cells as well as which tissues it accumulates in before clearance.…”