Complessi Metallo-Organici caricati con Coloranti Squarainici come nanosensibilizzatori per la Terapia Fotodinamica

Photodynamic therapy (PDT) has emerged as a promising biomedical approach for cancer treatment, antimicrobial applications, and addressing skin disorders. It is based on the use of photosensitizers (PSs), molecules that, after being excited by light at a specific wavelength, react with molecular oxygen to create reactive oxygen species (ROS). This reaction, if it occurs in the target tissue, causes cell death by apoptosis, necrosis, and autophagy. It has been shown that the efficacy of PDT is closely related to the characteristics of the PS, such as the ability to produce ROS, the ability to accumulate in the target tissue, biocompatibility, absorption in the therapeutic window (600-900nm), stability in serum or plasma, and fast elimination by the body; research in recent years has therefore focused on improving photosensitizers to allow greater efficacy and fewer side effects. In this thesis project, two squaraines (SQ2, SQ3) dyes, belonging to the class of polymethine dyes, were considered as potential PS. In fact, squaraine (SQ) dyes have been proved to show excellent photophysical and photochemical properties such as sharp and intense absorption bands and narrow emission bands with high extinction coefficients in the red and near-infrared region (NIR), low dark toxicity and side effects, good photo and thermal stability and a strong fluorescent emission in organic solvents. However, their tendency to self-aggregate in biological environments limits their PDT applicability. To address this, the squaraines were incorporated into three distinct Metal Organic-Frameworks -MOFs- (HPU-9(H), HPU-9(OH), and HPU-9(Br)), three-dimensional crystalline structures consisting of metal ions and organic ligands. The research involved characterization of the squaraine dyes and MOFs, followed by the assessment of MOF+SQ complexes to determine their stability, ROS production, and efficacy in comparison to free squaraine dyes. Finally, cytotoxicity and photoactivity tests were conducted using PANC-1 cells to evaluate the impact of these complexes on cellular systems. The results indicated successful incorporation of squaraines into MOFs, potentially mitigating the self-aggregation issue. The characterized MOF+SQ complexes demonstrated comparable stability and ROS production to free squaraine. The assessments of cytotoxicity conducted on PANC-1 cells have revealed the non-toxic nature of both MOF and MOF+SQ systems, while photoactivity assays revealed the promising photoactive effect of the HPU-9(Br)+SQ2 complex. This research contributes valuable insights into the development of advanced PDT formulations with improved stability and reduced side effects, paving the way for innovative therapeutic strategies in cancer treatment and beyond. Moving forward, since the conducted cellular tests serve as preliminary assessments, it is imperative to extend the project through additional in vitro testing on different cell types.