Design and Study of Hybrid Multifunctional Nanoparticles for Cancer Diagnostic and Treatment Through Spectral Photo Counting Scanner CT and X-Rays Activated PDT

<b>General context</b><br/>Cancer is one of the major societal issues of the century . Even if several strategies of treatments exist, the conditions of life of the patient during and after the treatment are deteriorated by side effects of heavy therapies such as radiotherapy (use of X rays of High energy). The need to propose new strategies of therapies is therefore of great interest.<br/><b>Introduction</b><br/>We are aiming at a technology that will ensure efficient treatment of cancer with low side effects, allow to perform accurate diagnostic and give access to in situ monitoring of the treatment. Our goal is based on the association of two cutting-edge technologies: spectral photon counting scanner CT (SPCCT) which is a ground-breaking imaging modality and a new X-ray based treatment known as X-rays activated Photodynamic Therapy (X-PDT). The perfect match between these two technologies will be ensured with specifically designed nanoprobes probes acting both as contrast media and therapeutic agents(1).<br/><br/>The possibility to use new treatments such as XPDT is raising a great interest. PDT alone is a clinically approved cancer treatment but, the strong absorption of light by tissues limits its use to rather superficial tumors. X-PDT is a new technology involving the same mechanisms but spreading the potential of this treatment. The principle of XPDT is to irradiate with low energy X-Rays hybrid nanoprobes consisting in an inorganic core functionalized with organic moieties (Photosensitizers-PS). Upon excitation the inorganic particle will emits light (scintillation) which will be absorbed by the PS. The latter will reach an excited state, making it able to react with surrounding oxygen and leading to the production of reactive oxygen species able to kill tumor cells.(2)<br/><br/>Spectral Photon Counting Computed Tomography (SPCCT) is a new imaging modality, currently in development. The SPCCT scanner is an evolution of the conventional CT scanner, with a totally new type of detection chain designed to provide high count-rate capabilities while offering energy discrimination with high spatial resolution. Its main asset is the ability to map and quantify elements based on their K-edge. For that modality, the traditional iodine based contrast agents are not particularly suited due to iodine’s K-edge being outside the clinical X-ray spectrum, the use of new types of contrast agents is therefore necessary. (3)<br/><b>Results</b><br/>Based on our previous works on the design and surface modification of lanthanide fluoride nanocrystals (4) we describe the design of hybrid terbium (III)-doped gadolinium fluoride nanoparticles (NPs) which act as contrast media for spectral CT scanner and show scintillation properties (emission of light under low energy X-rays excitation). These nanoparticles can be considered as interesting nanoplatforms for further development related to X-Rays based imaging and treatment.<br/>This presentation will first aim to highlight the results obtained concerning the luminescent properties of NPs under UV and X-ray excitation and their properties as contrast agent for spectral CT scanner (5). It will also describe the different strategies of surface modification for biocompatiblity and their effects on the optical properties of NPs. The proof of concept of the use of the nanoparticles as contrast agent in vivo as well as their ability to emit light when submitted to X-rays will be demonstrated. Finally, the functionalization of NPs by a PS will be discussed and results about in cellulo studies and singlet oxygen generation will be described.<br/><b>Bibliography</b><br/>(1) https://www.scanntreat.eu/<br/>(2) A. Bellanova et al., Photochem. Photobiol. sci., 2020, 19, 1134.<br/>(3) S. Si-mohamed et al., J. Clin. Med., 2021, 24, 5757.<br/>(4) F. Chaput, et al., Langmuir (2011), 27, 5555. / S. Karpati et al., Nanoscale 2020, 13, 3767. / A.L. Bulin et al., Adv. Sci., 2020, 7, 2001675. / V. Hubert et al., Adv. Sci, 2021, 17, 2101433 /<br/>(5) N. Halttunen et al., Scientific Reports (2019), 9, 12090