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

• Published in: Biomaterials 2012-05, Vol.33 (13), p.3560-3567
• Main Authors: Lee, Yi-Cheng, Chen, Der-Yow, Dodd, Stephen J, Bouraoud, Nadia, Koretsky, Alan P, Krishnan, Kannan M
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Animals; Brain - drug effects; Coated Materials, Biocompatible - pharmacology; Contrast agent; Dentistry; Echo-Planar Imaging; Female; Half-Life; Hydrogen-Ion Concentration - drug effects; Injections; Magnetic Resonance Imaging - methods; Male; Manganese Compounds - administration & dosage; Manganese Compounds - pharmacology; Manganese enhanced MRI; Mice; MnO nanoparticle; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Oxides - administration & dosage; Oxides - pharmacology; pH-responsive; Physiological Phenomena - drug effects; Rats; Rats, Sprague-Dawley; Silicon Dioxide - administration & dosage; Silicon Dioxide - pharmacology; Tail - drug effects; Time Factors
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2012.01.062

Abstract MnO nanoparticles have been tested to engineer a delayed increase in MRI T1 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 T1 relaxivity at pH 7.4, a pH where MnO does not dissolve into Mn2+ ions. The rate of dissolution and release of Mn2+ of the different coated MnO particles as well as changes in T1 relaxivity were measured at pH 5, a pH routinely obtained in the endosomal-lysosomal pathway. Of a number of coatings, silica coated MnO (MnO@SiO2 ) had the lowest relaxivity at pH 7.4 (0.29 m m−1  sec−1 ). About one third of the MnO dissolved within 20 min and the T1 relaxivity increased to that of free Mn2+ (6.10 m m−1  sec−1 ) after three days at pH 5. MRI of MnO@SiO2 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 Mn2+ . Intravenous infusion of MnO@SiO2 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 Mn2+ ions into the gallbladder. The MnO@SiO2 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.