Targeted biodegradable dendritic MRI contrast agent for enhanced tumor imaging


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Abstract

Highly sensitive and safe contrast agents (CAs) are essential for magnetic resonance imaging (MRI) to achieve accurate tumor detection and imaging. Dendrimer-based macromolecular MRI contrast agents are advantageous owing to their tumor-targeting ability, enhanced imaging contrast and enlarged imaging window. However, most of them have drawbacks of non-degradability and thereby long-term retention in body and toxicity. Herein, a tumor-targeting biodegradable dendritic CA (DCA) (FA-PEG-G2-DTPA-Gd) was prepared from a polyester dendrimer conjugated with gadolinium (Gd) chelates and PEG chains with distal folic acid. The DCA had a high longitudinal relaxivity up to 17.1 mM−1 s−1, 4 times higher than the clinically used CA Magnevist. The MRI contrasted by FA-PEG-G2-DTPA-Gd outlined the inoculated tumor more clearly, and had much higher contrast enhancement for a much longer time than Magnevist. More importantly, the biodegradable FA-PEG-G2-DTPA-Gd gave much less Gd retentions in all the organs or tissues than non-degradable DCAs. Thus, the high efficiency in MRI contrast enhancement and low Gd retention merit it a promising CA for contrast enhanced tumor MRI.Graphical abstractA tumor-targeting biodegradable dendritic CA with high contrast enhancement in MRI of tumor and minimal long-term retention is prepared and evaluated in vivo.

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