Oligoethylenimine grafted PEGylated poly(aspartic acid) as a macromolecular contrast agent: properties and in vivo studies

PEGylated poly(aspartate-g-OEI) was developed as a magnetic resonance imaging probe. The PEG-PBLA block copolymer was prepared by the ring-opening polymerization of beta-benzyl-L-aspartate N-carboxy-anhydride (BLA-NCA) initiated by the terminal primary amino group of mPEG-NH2, followed by grafting with oligoethylenimine (OEI, M-w = 800) and Gd-DTPA. Compared to Gd-DTPA (4.42 mM(-1) s(-1)), PEG-p(Asp-OEI-DTPA-Gd) exhibited much higher T-1 relaxivity (19.03 mM(-1) s(-1)), up to 4.3 times higher than Gd-DTPA. No obvious cytotoxicity was observed from the WST assay and H&E analysis, which illustrated that this macromolecular contrast agent (mCA) exhibited excellent biocompatibility. Folic acid (FA) was further labeled onto the mCA to endow the mCA with targeting ability. During in vivo animal studies, the FA labeled MRI probes showed a significant signal intensity enhancement in the tumor during different time intervals and provided a long and efficient window time for MR examination. These results suggest that such mCAs are excellent candidates as magnetic resonance imaging (MRI) probes with high efficiency and safety