Functionalization of Metal Nanoparticles/2D Nanocrystals with Photosensitizers Giving Water Dispersed Nanosystems for Cancer Treatment Under Low Dose X-Ray Irradiation

The functionalization of nanomaterials for cancer treatments can improve their sensitivity and therapeutic efficiency, enabling to increase the stability in the body and achieve a remarkable theranostic ability.<br/><br/>Among cancer treatments, PhotoDynamic Therapy (PDT) is a well-known oncotherapy based on the light activation of a photosensitizer (PS) that produces reactive oxygen species (ROS), in particular singlet oxygen (1O2), highly cytotoxic, under light irradiation. The main two drawbacks of classical PDT are the very low penetration of visible or near infrared light into biological tissues and the hydrophobicity of most PSs in aqueous solution. Indeed, they form aggregates in aqueous environment thus lowering their efficiency since only the monomeric form is photoactive. In addition, they do not target only the diseased tissue when applying PDT.<br/><br/>To overcome the first limitation, the use of X-rays to reach deep-seated tumors is increasingly proposed in the literature. In this respect, here we present the functionalization of a novel patent-pending nanosystem (NS) made of multifunctional 2D nanocrystals able to convert low energy X-rays into reactive oxygen species and radiosensitizing agents to treat deep-seated cancers. The functionalization is performed with an ad-hoc modified photosensitizer derivative belonging to the class of porphyrins, that are the most useful class of PS employed in clinical PDT. The chemical route to obtain the novel multifunctional nanosystems is discussed and the successful organic-inorganic conjugation is confirmed by a comprehensive panel of characterization techniques, including morphological, structural and spectroscopic characterizations (UV-Vis, fluorescence, Raman, HRTEM/STEM, XPS). The potential of the nanosystems for biological applications for cancer treatment under low energy X-Ray irradiationare discussed.<br/><br/>Acknowledgment: This work has been funded by the Horizon Europe Project "PERSEUS" [EIC PATHFINDER grant number 101099423].