The Use of Silica Coated MnO Nanoparticles to Control MRI Relaxivity in Response to Specific Physiological Changes

MnO nanoparticles have been tested to engineer a delayed increase in MRI T ₁ relaxivity caused by cellular uptake via endocytosis into acidic compartments. Various coatings on core-shell structured MnO nanoparticles were tested for those that had the lowest T ₁ relaxivity at pH 7.4, a pH where MnO does not dissolve into Mn ²⁺ ions. The rate of dissolution and release of Mn ²⁺ of the different coated MnO particles as well as changes in T ₁ relaxivity were measured at pH 5, a pH routinely obtained in the endosomal-lysosomal pathway. Of a number of coatings, silica coated MnO (MnOSiO ₂) had the lowest relaxivity at pH 7.4 (0.29 mm ^-1 sec ^-1). About one third of the MnO dissolved within 20 min and the T ₁ relaxivity increased to that of free Mn ²⁺ (6.10 mm ^-1 sec ^-1) after three days at pH 5. MRI of MnOSiO ₂ particles injected into the rat brain showed time-dependent signal changes consistent with the in vitro rates. Thalamocortical tract-tracing could be observed due to the released Mn ²⁺. Intravenous infusion of MnOSiO ₂ particles showed little enhancement in any tissue except gallbladder. The gallbladder enhancement was interpreted to be due to endocytosis by liver cells and excretion of Mn ²⁺ ions into the gallbladder. The MnOSiO ₂ core-shell nanoparticles show the best potential for delaying the release of MRI contrast until endocytosis into low pH compartments activate MRI contrast. The delayed enhancement may have benefits for targeting MRI contrast to specific cells and surface receptors that are known to be recycled by endocytosis.