Functional Chrysotile Nanotubes for Photodynamic Therapy

The aim of our work is the development of multicomponent photodynamic therapy (PDT) agents by coupling scintillating chrysotile nanotubes (NTs) with different conjugated photosensitizers (PS) anchored on their surfaces, with the ability to enhance the production of singlet oxygen (SO) in an aqueous environment under X-ray irradiation, that can oxidize and degrade biopolymers such as DNA and proteins. Thus, a system generating ROS can be capable of producing targeted local damage at the subcellular and/or molecular level, inducing the tumor cell death through oxidative damage of cellular membranes.<br/>In general, when ionizing radiation excites the nanoscintillator, instead of activating its luminescence, the absorbed energy is transferred to the PS through an energy-transfer process. A subsequent energy transfer to ground-state oxygen molecules in the aqueous environment promotes the creation of the singlet oxygen species.<br/>We employ synthetic chrysotile NTs as nanoscintillators because these nanostructures in their stoichiometric form are highly biocompatible particles, that can be easy prepared in aqueous solution, under hydrothermal conditions in the presence of Mg and Si precursors. The outer surface of NTs is brucitic and in aqueous environment is modified by concentrating Mg²⁺ ions towards the surface, giving rise to a positive Z-potential. This property allows to bind to the surface a number of anionic chemical species, including our selected PS dyes.<br/>In particular, the NTs functionalized with the H₂TPPS₄− porphyrin have been successfully tested in vitro as X-PDT agents in human glioblastoma primary cells (U-87). The results of the in vitro tests indicate that the functionalized NTs, thanks to increased energy release given by their interaction with high-energy radiation and to the sensitized production of cytotoxic ROS, help to both (i) promptly kill the tumorigenic cells by boosting the thermal shock and (ii) limit their reproduction by favouring the triggering of the apoptosis mechanism [1,2].<br/>[1] I. Villa, C. Villa, R. Crapanzano, V. Secchi, M. Tawfilas, E. Trombetta, L. Porretti, A. Brambilla, M. Campione, Y. Torrente, A. Vedda, and A. Monguzzi, ACS Applied Materials & Interfaces 2021 13 (11), 12997-13008<br/>[2] C. Villa, M. Campione, B. Santiago-González, F. Alessandrini, S. Erratico, I. Zucca, M.G. Bruzzone, L. Forzenigo, P. Malatesta, M. Mauri, E. Trombetta, S. Brovelli, Y. Torrente, F. Meinardi, A. Monguzzi, A., Adv. Funct. Mater. 2018, 28, 1707582.