Hybrid Nanosystems to Treat Deep-seated Tumors Under X-Ray Irradiation

Photodynamic therapy (PDT) is a clinical approach to treat cancer by activating a photosensitizer (PS) through light exposure ranging from UV to near-infrared. This activation induces the production of reactive oxygen species (ROS), particularly singlet oxygen (¹O₂), well known for its cytotoxic impact on cancer cells. Studies reported in the literature highlighted the possibility to enhance ¹O₂ production by combining photosensitizers with metal nanoparticles under laser irradiation. The main drawback of conventional PDT lies in the limited penetration of visible light in biological tissues, impeding effective photosensitizer excitation in deeper tissues. Consequently, substantial efforts have been directed towards overcoming this limitation through X-ray irradiation. Metal nanoparticles with elevated Z values exhibit efficient X-ray absorption, facilitating energy delivery to surrounding tissues¹. It has been reported that the presence of photosensitizers onto metal nanoparticles (NPs) could enhance their ¹O₂ and ROS generation. In particular, Gold nanoparticles (AuNPs) have gained prominence due to their biocompatibility, making them widely used as contrast agents.

This study presents the synthesis of new hybrid nanosystems realized by conjugating rose bengal (RB) derivatives, prepared by reacting a proper linker with the RB carboxylic moiety, to AuNPs. An effective binding was obtained and the ability of the nanosystems to produce ¹O₂ and ROS under irradiation was demonstrated. Preliminary biological tests were performed, demonstrating the efficacy of a nanosystem-mediated X-Ray triggered treatment.

Acknowledgment: This work has been funded by the Horizon Europe Project "PERSEUS" [grant number 101099423].

S. J. McMahon, W. B. Hyland, M. F. Muir, J. A. Coulter, S. Jain, K. T. Butterworth, G. Schettino, G. R. Dickson, A.R. Hounsell, J. M. O’Sullivan, K. M. Prise, D. G. Hirst, F. J. Currell, Sci Rep 2011, 1, 18.