Targeted gadolinium-loaded dendrimer nanoparticles for tumor-specific magnetic resonance contrast enhancement
International Journal of Nanomedicine
A target-specifi c MRI contrast agent for tumor cells expressing high affi nity folate receptor was synthesized using generation fi ve (G5) of polyamidoamine (PAMAM) dendrimer. Surface modifi ed dendrimer was functionalized for targeting with folic acid (FA) and the remaining terminal primary amines of the dendrimer were conjugated with the bifunctional NCS-DOTA chelator that forms stable complexes with gadolinium (Gd III). Dendrimer-DOTA conjugates were then complexed with GdCl 3, followed by
... dCl 3, followed by ICP-OES as well as MRI measurement of their longitudinal relaxivity (T1 s −1 mM −1 ) of water. In xenograft tumors established in immunodefi cient (SCID) mice with KB human epithelial cancer cells expressing folate receptor (FAR), the 3D MRI results showed specifi c and statistically signifi cant signal enhancement in tumors generated with targeted Gd(III)-DOTA-G5-FA compared with signal generated by non-targeted Gd(III)-DOTA-G5 contrast nanoparticle. The targeted dendrimer contrast nanoparticles infi ltrated tumor and were retained in tumor cells up to 48 hours post-injection of targeted contrast nanoparticle. The presence of folic acid on the dendrimer resulted in specifi c delivery of the nanoparticle to tissues and xenograft tumor cells expressing folate receptor in vivo. We present the specifi city of the dendrimer nanoparticles for targeted cancer imaging with the prolonged clearance time compared with the current clinically approved gadodiamide (Omniscan TM ) contrast agent. Potential application of this approach may include determination of the folate receptor status of tumors and monitoring of drug therapy.