Transition metal complexes of purpose-­‐tailored biocompatible and biodegradable polymers for imaging and therapy

Poly(amidoamine)s (PAAs) are a family of synthetic polymers obtained by Michael-type polyaddition of amines to bisacrylamides. Their polymer chain contains tert-amino and amido groups in regular succession. In addition, many reactive functional groups can be introduced as side substituents.1 Several PAAs have been shown to possess a remarkable potential for biomedical applications in that they are biodegradable and biocompatible, and owing to their versatility can be tailored to specific applications. In particular, amphoteric PAAs, which in extra cellular fluids (pH 7.4) are zwitterionic but predominantly anionic, are highly biocompatible and exhibit a “stealth-like” behavior, that is, after intravenous injection in test animals are not captured by the reticulo-endothelial system and have a prolonged permanence in the blood circle. They tend to aggregate in water solutions in the form of small nanoparticles with hydrodynamic diameters in the range of 5−20 nm,2 and in tumor-bearing animals, they are passively concentrated in the tumor tissues by the so-called EPR (enhanced permeation and retention) effect.3 They are therefore very attractive as carriers for molecular complexes. For this purpose our attention was captured by the possibility to synthesize poly(amidoamine) copolymers bearing in the minor repeating unit a suitable chelating pendent. In this context, the presentation intends to show the most significant results obtained in the last years (Figure 1), which have led to the preparation of rhenium, ruthenium, iridium and gadolinium polymer complexes, as optical imaging probes, γ and β emitter probes (for SPECT imaging and therapy, respectively), photodynamic therapy (PDT) agents, and T1 and T2 relaxing agents for magnetic resonance imaging (MRI).