Carbodiimide versus Click Chemistry for Nanoparticle Surface Functionalization: A Comparative Study for the Elaboration of Multimodal Superparamagnetic Nanoparticles Targeting αvβ3 Integrins

Superparamagnetic fluorescent nanoparticles targeting alpha(v)beta(3) integrins were elaborated using two methodologies: carbodiimide coupling and click chemistries (CuACC and thiolyne). The nanoparticles are first functionalized with hydroxymethylenebisphonates (HMBP) bearing carboxylic acid or alkyne functions. Then, a large number of these reactives functions were used for the covalent coupling of dyes, poly(ethylene glycol) (PEG), and cyclic RGD. Several methods were used to characterize the nanoparticle surface functionalization, and the magnetic properties of these contrast agents were studied using a 1.5 T clinical MRI. The affinity toward integrins was evidenced by solid-phase receptor-binding assay. In addition to their chemoselective natures, click reactions were shown to be far more efficient than the carbodiimide coupling. The grafting increase was shown to enhance targeting affinity to integrin without imparing MRI and fluorescent properties.