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.

A Biomimetic Emitter Inspired from Green Fluorescent Protein.

The unique tripeptide structure of green fluorescent protein (GFP), a Ser-Tyr-Gly motif, generates the mature chromophore in situ to define the emission profiles of GFP. Here, we describe the rational design and discovery of a biomimetic fluorescent emitter, MBP, by mimicking the key structure of the Ser-Tyr-Gly motif. Through systematically tailoring the tripeptide, a family of four chromophores were engineered, while only MBP exhibited bright fluorescence in different fluid solvents with highly enhanced quantum yields. Distinct to previous hydrogen-bonding-induced fluorescence quenching of GFP chromophore analogues, the emission of MBP was only slightly decreased in protic solvents. Heteronuclear multiple bond correlation techniques demonstrated the fundamental mechanism for enhanced fluorescence emission owing to the synergy of the formation of the intramolecular hydrogen-bonding-ring structure and the self-restricted effect, which was further illustrated via theoretical calculations. This work puts forward an extraordinary approach toward highly emissive biomimicking fluorophores, which gives new insights into the emission mechanisms and photophysics of GFP-like chromophores.

Multifunctional nanoprobes for macrophage imaging.

Imaging and tracking macrophage behaviors in vivo are essential to reveal its biological function and fate in various diseases. Small molecular probes suffer from poor macrophage targeting and retention, rapid clearance, and deficient metabolizing stability. To overcome these limitations, a variety of functional nanoprobes have been developed for targeted imaging of macrophages in divergent diseases such as cancer, atherosclerosis and obesity. Generally, nanoprobes are functionalized with targeting peptides, ligands or antibodies to fulfill high macrophage affinity. In this review, the most recent advances of nanoprobes for imaging macrophages in vivo and ex vivo are systematically summarized. The challenges and perspectives of precisely imaging macrophages with improved signal-to-background ratios via nanoprobes are further discussed.