Polyamidoamines (PAAs) are a class of water-soluble and biocompatible polymers obtained by a Michael-type polyaddition of primary or secondary amines with bisacrylamides. Their synthesis is highly versatile, as they can be easily designed to possess linear, grafted or hyperbranched architecture and to bear various chemical functions. Thus, PAAs can be exploited for various biomedical applications, as antibacterial, antiviral, antimalarial or antitumoral agents [1]. In the recent past, polyamidoamine based-copolymers, bearing a phenanthroline pendant in the minority part, were proposed as polymer complexing agents able to chelate Re, Ir and Ru metal fragments, giving rise to the formation of luminescent biocompatible polymers [2-4].

The Ru(II)-based polyimino-complexes are known to be efficient photosensitizers upon a proper light irradiation for the singlet oxygen generation, which is a powerful cytotoxic agent exploited in the so called photodyamic therapy (PDT).

In particular, a polyamidoamine complex named Ru-PhenAN, which was internalized by cells via active mechanisms of endocytosis, was found to be able to escape the endolysosomal compartments upon irradiation and accumulate at the nuclear level, which would possibly cause its higher photocytotoxicity [5]. However, the main drawback of PhenAN was the difficult multi-step synthesis required to obtain the BAP molecule, starting from the expensive 4-methyl-1,10-phenantroline, and thus in this work, a new synthetic route to obtain a PAA analogous to PhenAN, named PhenVS, and in which the phenanthroline moiety derives from a more easily and cheaper obtainable molecule, was developed (Fig. 1).

The final goal of this work was the obtainment of an organic-inorganic nanohybrid derived by the functionalization of gold nanostars (GNS) with the polyamidoamine-Ru(II) complex (Fig. 2) combining the antitumoral action based on PDT due to Ru(II) properties with plasmon photothermal therapy (PPTT) due to the inorganic core.

In this communication, the synthesis of the new copolymer, its complexation with suitable Ru(II) fragments, as well as the preparation of the GNS and the decoration of their surface with multilayer of polyamidoamines through a layer-by-layer approach will be presented. Finally, their properties will be shown together with some biological assays carried out in vitro on HeLa cells. The results demonstrate that the combination with the gold nanostars enhanced the toxicity induced by the Ru complex upon illumination. Ongoing studies are focused on optimizing the nanohybrid design in order to further enhance the combined efficacy.

References

1- E. Ranucci, A. Manfredi Chemistry Africa 2019, 2, 167.

2- D. Maggioni, F. Fenili, L. D’Alfonso, D. Donghi, M. Panigati, I. Zanoni, R. Marzi, A. Manfredi, P. Ferruti, G. Alfonso, E. Ranucci, Inorg. Chem. 2012, 51, 12776.

3- D. Maggioni, M. Galli, L. D’Alfonso, D. Inverso, M. V. Dozzi, L. Sironi, M. Iannacone, M. Collini, P. Ferruti, E. Ranucci, G. D’Alfonso Inorg. Chem. 2015, 54, 544.

4- L. Mascheroni, M.V. Dozzi, E. Ranucci, P. Ferruti, V. Francia, A. Salvati, D. Maggioni Inorg. Chem. 2019, 58, 14586.

5- L. Mascheroni, V. Francia, B. Rossotti, E. Ranucci, P. Ferruti, D. Maggioni, A. Salvati ACS Appl. Mater. Interfaces 2020, 12, 34576.

Acknowledgments

D.M. acknowledges financial support by Università degli Studi di Milano (PSR2025_DIP_005_PI_GDICA)