title: Multifunctional mesoporous silica nanospheres with cleavable Gd(III) chelates as MRI contrast agents: synthesis, characterization, target-specificity, and renal clearance.
abstract: Mesoporous silica nanospheres (MSNs) are a promising material for magnetic resonance imaging (MRI) contrast agents. In this paper multifunctional MSNs with cleavable Gd(III) chelates are synthesized and characterized, and their applicability as MRI contrast agents is demonstrated both in vitro and in vivo. The MSNs contain Gd(III) chelates that are covalently linked via a redox-responsive disulfide moiety. The MSNs are further functionalized with polyethylene glycol (PEG) and an anisamide ligand to improve their biocompatibility and target specificity. The effectiveness of MSNs as an MRI imaging contrast agent and their targeting ability are successfully demonstrated in vitro using human colon adenocarcinoma and pancreatic cancer cells. Finally, the capability of this platform as an in vivo MRI contrast agent is tested using a 3T scanner. The Gd(III) chelate was quickly cleaved by the blood pool thiols and eliminated through the renal excretion pathway. Further tuning of the Gd(III) chelate release kinetics is needed before the MSN system can be used as target-specific MRI contrast agents in vivo.
authors: Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina, 27599, USA.
authors: Juan L
authors: JL
authors: Vivero-Escoto
authors: Kathryn M L
authors: KM
authors: Taylor-Pashow
authors: Rachel C
authors: RC
authors: Huxford
authors: Joseph
authors: J
authors: Della Rocca
authors: Christie
authors: C
authors: Okoruwa
authors: Hongyu
authors: H
authors: An
authors: Weili
authors: W
authors: Lin
authors: Wenbin
authors: W
authors: Lin
mesh_terms: D000818:Animals; D001549:Benzamides / Q000737:chemistry; D002614:Chelating Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry; D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry; D005260:Female; D005682:Gadolinium / Q000008:administration & dosage / Q000737:chemistry*; D019073:HT29 Cells; D006801:Humans; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D054118:Nanospheres / Q000737:chemistry* / Q000648:ultrastructure; D010084:Oxidation-Reduction; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D001549:Benzamides; D002614:Chelating Agents; D003287:Contrast Media; D011092:Polyethylene Glycols; D012822:Silicon Dioxide; D005682:Gadolinium