title: Gadolinium-coordinated elastic nanogels for in vivo tumor targeting and imaging.
abstract: Coordination polymer gels have been recognized as promising hybrid nanoplatforms for imaging and therapeutic applications. Here we report functional metal-organic coordinated nanogels (GdNGs) for in vivo tumor imaging, whose non-crystalline and elastic nature allows for long blood circulation, as opposed to the rapid systemic clearance of common nanohybrids with rigid/crystalline frameworks. The deformable structure of GdNGs was constructed by random crosslinking of highly flexible polyethyleneimines (PEI) with gadolinium (Gd(3+)) coordination. The in vitro characterization revealed that GdNGs have elasticity with an apparent Young's modulus of 3.0 MPa as well as minimal cytotoxicity owing to the tight chelation of Gd(3+) ions. In contrast to common T1-enhancing gadolinium complexes, GdNGs showed the capability of enhancing negative T2 contrast (r2 = 82.6 mm(-1)s(-1)) due to the Gd(3+)-concentrated nanostructure. Systemic administration of fluorescently labeled GdNGs with core and overall hydrodynamic sizes of ~65 and ~160 nm manifested efficient targeting and dual-modality (magnetic resonance/fluorescence) imaging of tumor in a mouse model. The minimal filtration by the reticuloendothelial system (RES) suggests that the structural deformability helps the large colloids circulate in the blood stream for tumor accumulation. The unusual performance of a large Gd(3+)-complexed colloid (minimal RES sequestration and high T2 contrast enhancement) represents the versatile nature of nanoscopic organic-inorganic hybridization for biomedical applications.
authors.affiliation: Center for Theragnosis, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, South Korea.
authors.forename: Chang-Keun
authors.initials: CK
authors.lastname: Lim
authors.forename: Ajay
authors.initials: A
authors.lastname: Singh
authors.forename: Jeongyun
authors.initials: J
authors.lastname: Heo
authors.forename: Daehong
authors.initials: D
authors.lastname: Kim
authors.forename: Kyung Eun
authors.initials: KE
authors.lastname: Lee
authors.forename: Hyesung
authors.initials: H
authors.lastname: Jeon
authors.forename: Joonseok
authors.initials: J
authors.lastname: Koh
authors.forename: Ick-Chan
authors.initials: IC
authors.lastname: Kwon
authors.forename: Sehoon
authors.initials: S
authors.lastname: Kim
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry*; D003952:Diagnostic Imaging / Q000379:methods*; D005682:Gadolinium / Q000737:chemistry*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D000080385:Nanogels; D009369:Neoplasms / Q000175:diagnosis*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*
chemical_list: D003287:Contrast Media; D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D005682:Gadolinium