Design of a biocompatible probe for theranostic and multimodal imaging applications

Multimodal imaging probes can provide diagnostic information combining different imaging modalities. Nanoparticles (NPs) can contain two or more imaging tracers that allow several diagnostic techniques to be used simultaneously. In this thesis, a complex coacervation process to produce core-shell completely biocompatible polymeric nanoparticles (HyCoS) for multimodal imaging applications is described. Innovations on the traditional coacervation process are found in the control of the reaction temperature, allowing a speeding up of the reaction itself, and the production of a double-crosslinked system to improve the stability of the nanostructures in the presence of a clinical relevant contrast agent for MRI (Gd-DTPA). Through the control of the crosslinking behavior, an increase up to 6 times of the relaxometric properties of the Gd-DTPAis achieved. Furthermore, HyCoS can be loaded with a high amount of dye such as ATTO 633 or conjugated with a model dye such as FITC for in vivo optical imaging. The results show stable core-shell polymeric nanoparticles that can be used both for MRI and for optical applications allowing detection free from harmful radiation. Additionally, preliminary results about the possibility to trigger the release of a drug through a pH effect are reported. Furthermore, NPs combined with peptides, allow an efficient in vivo targeting useful to improve drug delivery and clinical outcome. We report the in vivo targeting of aggressive A20 murine B-cell lymphoma by idiotype-specific peptide pA20-36 using fluorescence molecular tomographic (FMT) imaging in xenograft mouse models of lymphoma A20, through VivoTag probe, an amine-reactive near-infrared fluorochrome. In the end, core-shell polymeric nanovector with improved relaxometric properties for simultaneous PET/MRI acquisitions. and 18F-FDG is used as tracer for PET. A protocol for sorption of 18F-FDG into the nanoparticles is studied and designed to be integrated downstream the production of the tracer.