Folic acid conjugated chitosan derivative for tumor targeted magnetic resonance imaging
Contrast agents with high efficiency and safety are excellent candidates as magnetic resonance imaging probes. In this study, a nanoparticle contrast agent based on chitosan was synthesized. The backbone was chitosan, and the side chains were low molecular oligoethylenimine, which possessed multiple primary amines to increase the grafting number of Gd DTPA per glucose ring. This macromolecular chitosan derivative covalently conjugated with folic acid offers a high loading density of Gd DTPA with targeting capacity. The r1 value was found to be 25.9 mM s, which was 5.4 times higher than Magnevist. The higher r1 value was mainly due to the increased rotational correlation time (tR) after conjugation of DTPA Gd onto chitosan chain and the increased loading density of Gd permolecule. No obvious cytotoxicitywas observed fromWSTassay,which illustrated that the chitosan derivative exhibited excellent biocompatibility. During in vivo animal studies, the probe provided better signal intensity enhancement in the tumor after 5 h post injection. This study demonstrated that the developed oligoethylenimine grafted chitosan route was effective to increase the loading density of Gd and then significantly enhanced the relaxivity of the macromolecular contrast probes. Such an oligoethylenimine grafted chitosan derivative has great potential for developing sensitive and biocompatible MRI probe with targeting capability.