Synthesis And Characterization Of Novel MRI Contrast Agents Targeting Tumor

Early diagnosis of tumor are essential for successful cancer therapy. Magnetic resonance imaging (MRI), characterized by a remarkable spatial resolution, is widely used for anatomical and functional imaging of diseased tissues. MRI contrast agents (CAs) have played an important role for improving the image quality by enhancing the image contrast differences between normal and diseased tissues.Precisely nano structured dendritic contrast agents (DCAs) with high longitudinal relaxivity (r1) and passive targeting tumor capability via the enhanced permeability and retention (EPR) effect have shown great potentials in tumor detection and diagnosis. However, their applications were hindered by their non-biodegradability and difficulty in synthesis. In this paper, DCAs (G1-G5) based on biodegradable polyester dendrimers were synthesized and characterized. Their rls increased with their molecular weights from10.2to17.5mM-1S-1, about2.4to4.1times higher than that of DTPA-Gd. The DCAs were stable at acidic pH, but hydrolyzed rapidly at physiological pH, which rendered the DCA’s Gd-long-term retention as low as that of small molecular CAs. The in vivo MRI study suggested that the biodegradable DCA at lower generation (G2-DTPA-Gd) was more suitable for tumor imaging, while the one at higher generation (G5-DTPA-Gd) was good for liver imaging.In this study, a linear polylysine tumor-targeted contrast agents was exploited by conjugating small molecular imaging agent, fluorescent molecule and targeting agents to terminal amino groups of polylysine. This high targeting specificity is on the basis of selective binding of boronic acids to sialic acide residues of tumor cell. DCA attached to the free amino-groups of Rhodamine-labeled tumor-targeted contrast agents. The DCA-polylysine was negatively charged in physiology pH, however, it turned positively charged when the pH was lower than6. And we could use this charge reversal concept to kill tumor cells. The results of confocal characteristics suggested that relatively higher membrane adsorption of5%-B compared to1%-B. These results demonstrated the specific binding of boronic acid to tumor cells. This polylysine contrast agent can be a promising tumor-targeted probe for cancer diagnosis.