T2-Weighted Magnetic Resonance Imaging of Hepatic Tumor Guided by SPIO-Loaded Nanostructured Lipid Carriers and Ferritin Reporter Genes.

Abstract

Nowadays, there is a high demand for supersensitive contrast agents for the early diagnostics of hepatocarcinoma. It has been recognized that accurate imaging information is able to be achieved by constructing hepatic tumor specific targeting probes, though it still faces challenges. Here, a AGKGTPSLETTP peptide (A54)-functionalized superparamagnetic iron oxide (SPIO)-loaded nanostructured lipid carrier (A54-SNLC), which can be specifically uptaken by hepatoma carcinoma cell (Bel-7402) and exhibited ultralow imaging signal intensity with varied Fe concentration on T2-weighted imaging (T2WI), was first prepared as an effective gene carrier. Then, an endogenous ferritin reporter gene for magnetic resonance imaging (MRI) with tumor-specific promoter (AFP-promoter) was designed, which can also exhibit a decrease in signal intensity on T2WI. At last, using protamine as a cationic mediator, novel ternary nanoparticle of A54-SNLC/protamine/DNA (A54-SNPD) as an active dual-target T2-weighted MRI contrast agent for imaging hepatic tumor was achieved. Owing to the synergistic effect of A54-SNLC and AFP-promoted DNA targeting with Bel-7402 cells, T2 imaging intensity values of hepatic tumors were successfully decreased via the T2 contrast enhancement of ternary nanoparticles. It is emphasized that the novel A54-SNPD ternary nanoparticle as active dual-target T2-weighted MRI contrast agent were able to greatly increase the diagnostic sensitivity and specificity of hepatic cancer.