Gadolinium-coordinated elastic nanogels for invivo tumor targeting and imaging

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 invivo 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 (Gd³⁺) coordination. The invitro characterization revealed that GdNGs have elasticity with an apparent Young's modulus of 3.0MPa as well as minimal cytotoxicity owing to the tight chelation of Gd³⁺ ions. In contrast to common T₁-enhancing gadolinium complexes, GdNGs showed the capability of enhancing negative T₂ contrast (r₂=82.6mm^-1s^-1) due to the Gd³⁺-concentrated nanostructure. Systemic administration of fluorescently labeled GdNGs with core and overall hydrodynamic sizes of ~65 and ~160nm 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 Gd³⁺-complexed colloid (minimal RES sequestration and high T₂ contrast enhancement) represents the versatile nature of nanoscopic organic-inorganic hybridization for biomedical applications.