Mn(2+)-doped silica nanoparticles for hepatocyte-targeted detection of liver cancer in T1-weighted MRI.

With an aim to examine the possibility of developing a liver-specific MRI contrast agent that takes advantages of brightly enhanced MR images by Mn²⁺ whilst making up the limitations of the pre-developed contrast agent, the Mn²⁺-doped SiO₂ nanoparticles (Mn-SiO₂) were synthesized and their characteristics as MR contrast agents were investigated. The in vitro and in vivo investigations showed that Mn-SiO₂ has unique MR contrast-enhancing characteristics that activate positive contrast enhancement in T1-weighted MR images only under low pH conditions by liberating Mn²⁺ ions from MR inactive nanoparticles. The administration of Mn-SiO₂ to an orthotopic xenograft model of human hepatocellular carcinoma (HCC) resulted in a differentiation of enhancement periods between HCC and normal parenchyma tissues on T1-weighted MR images and consequently presented the duplicates of the highly contrast-enhanced liver image with an equal liver-to-HCC contrast ratio but opposite contrast. The Mn-SiO₂-enhanced MR imaging therefore allowed for the repetitive detection of the HCC within a single MR imaging session, which can help us to achieve more reliable diagnosis and characterization of liver lesions than is possible with any currently used Mn²⁺-based contrast agent. In addition, the in vivo biodistribution study also supported the effectiveness of Mn-SiO₂ nanoparticles as a liver-specific MRI contrast agent, which efficiently delivers and releases the T1-contrasting Mn²⁺ ions to targeted hepatocytes.