Differential characterization of hepatic tumors in MR imaging by burst-released Mn²⁺-ions from hollow manganese-silicate nanoparticles in the liver

Gd³⁺-based contrast agents monopolize in the clinical MR imaging-based diagnosis of hepatic tumors, however, the inherent toxicity by the released Gd³⁺-ions triggered an urgent demand for safer alternatives. Here, we demonstrate hollow manganese silicate nanoparticles (HMS), which exert burst-release of Mn²⁺-ions by switching to physiological acidic condition, exhibiting high effectiveness in hepatic tumor characterization as liver-specific MR contrast agent through the in-depth in vivo MR imaging study and immunohistochemical investigations with three hepatic tumor models (e.g., hepatocellular carcinoma, neuroendocrine carcinoma, adenocarcinoma). Their characteristic time-sequential enhancement patterns in HMS-enhanced MR imaging with improved conspicuity reflect their biological features such as vascularity, cellularity, mitochondrial activity and hepatocellular specificity, and thus allow the disease-specific characterization of various hepatic tumors. HMS-enhanced MR imaging with necrotic hepatocellular carcinoma model suggested the good correlation of the extent of tumor necrosis with residual mitochondrial activity. Such multi-responsive spatio-biological distribution and function of HMS resulting in time-dependent bioimaging coupled with low systemic toxicity sets the clinical potential to accurate diagnosis and therapeutic response in various hepatic tumors.