An ASGP-R-targeting magnetic resonance imaging contrast agent for liver cancer diagnosis†

Development of novel Gd-based contrast agents for targeted magnetic resonance imaging (MRI) of liver cancer remains a great challenge. Herein we reported a novel Gd-based MRI contrast agent with improved relaxivity for specifically diagnosing liver cancer. This GSH-responsive macromolecular contrast agent (mCA), POLDGd, was prepared by RAFT polymerization, and its lactic acid moiety could precisely target the ASGP-R surface protein on liver cancer cells, whereas PODGd without the lactic acid moiety was prepared as a control. POLDGd had a high molecular weight of 45 kDa and a particle size of 103 nm. Its longitudinal relaxivity (11.39 mM⁻¹ s⁻¹) measured via a 3.0 T MR scanner was three times that of the clinically used contrast agent DTPA-Gd. In comparison with the PODGd-treated group, the signal enhancement at the tumor site was significantly prolonged, with a maximum enhancement peak of about 190% after intravenous injection of POLDGd into tumor-bearing mice. A high accumulation level of POLDGd in the liver tumors observed via MRI was also confirmed by fluorescence imaging. POLDGd showed minimal side effects, which may be ascribed to its metabolism through the kidneys. Therefore, POLDGd may be used as a highly effective biosafe nanoscale contrast agent for targeted MRI of liver cancer.