Liver-targeting MRI contrast agent based on galactose functionalized o-carboxymethyl chitosan.

Commercial gadolinium (Gd)-based contrast agents (GBCAs) play important role in clinical diagnostic of hepatocellular carcinoma, but their diagnostic efficacy remained improved. As small molecules, the imaging contrast and window of GBCAs is limited by low liver targeting and retention. Herein, we developed a liver-targeting gadolinium (Ⅲ) chelated macromolecular MRI contrast agent based on galactose functionalized o-carboxymethyl chitosan, namely, CS-Ga-(Gd-DTPA)n, to improve hepatocyte uptake and liver retention. Compared to Gd-DTPA and non-specific macromolecular agent CS-(Gd-DTPA)n, CS-Ga-(Gd-DTPA)n showed higher hepatocyte uptake, excellent cell and blood biocompatibility in vitro. Furthermore, CS-Ga-(Gd-DTPA)n also exhibited higher relaxivity in vitro, prolonged retention and better T1-weighted signal enhancement in liver. At 10 days post-injection of CS-Ga-(Gd-DTPA)n at a dose of 0.03 mM Gd/Kg, Gd had a little accumulation in liver with no liver function damage. The good performance of CS-Ga-(Gd-DTPA)n gives great confidence in developing liver-specifc MRI contrast agents for clinical translation.

Multifunctional polysaccharide nanoprobes for biological imaging.

Imaging and tracking biological targets or processes play an important role in revealing molecular mechanisms and disease states. Bioimaging via optical, nuclear, or magnetic resonance techniques enables high resolution, high sensitivity, and high depth imaging from the whole animal down to single cells via advanced functional nanoprobes. To overcome the limitations of single-modality imaging, multimodality nanoprobes have been engineered with a variety of imaging modalities and functionalities. Polysaccharides are sugar-containing bioactive polymers with superior biocompatibility, biodegradability, and solubility. The combination of polysaccharides with single or multiple contrast agents facilitates the development of novel nanoprobes with enhanced functions for biological imaging. Nanoprobes constructed with clinically applicable polysaccharides and contrast agents hold great potential for clinical translations. This review briefly introduces the basics of different imaging modalities and polysaccharides, then summarizes the recent progress of polysaccharide-based nanoprobes for biological imaging in various diseases, emphasizing bioimaging with optical, nuclear, and magnetic resonance techniques. The current issues and future directions regarding the development and applications of polysaccharide nanoprobes are further discussed.