Cyclodextrin-conjugated low-molecular-weight polyethyleneimine as a macromolecular contrast agent for tumor-targeted magnetic resonance imaging.

Macromolecular contrast agents (CAs) usually possess excellent contrast ability and tumor-targeting ability in comparison with small-molecule CAs, especially for early tumor detection. Herein, cyclodextrin-conjugated low-molecular-weight polyethyleneimine was synthesized as a macromolecular backbone. Afterward, a linear polymer with adamantane terminal and Gd chelates was synthesized, followed by conjugating with the backbone via host-guest interaction. Finally, folic acid was conjugated onto the as-prepared CAs through bioorthogonal chemistry, which endowed the CAs with the capability to accumulate into the tumor region. Compared to Magnevist ( r 1 = 4.25 mM -1 s -1 ) used in clinic, the PC/Ad-PEG 2000 -PLL(DTPA-Gd)-FA exhibited higher longitudinal relaxivity ( r 1 = 11.62 mM -1 s -1 ) with excellent biocompatibility. Furthermore, in vivo experiments demonstrated that PC/Ad-PEG 2000 -PLL(DTPA-Gd)-FA could effectively accumulate in the tumor region and produce a brighter image than that of Magnevist. The H&E staining and metabolic data further illustrated that this CA possessed excellent biocompatibility in vivo . Finally, these results above suggest that this macromolecular CA could be a potential candidate as a MRI CA for tumor-targeted diagnosis.