Sincrotró ALBA
Charles Bosson (Université Paris-Saclay, CNRS, Institut des Sciences Moléculaires d'Orsay, France)
Quan
Abstract
Radiotherapy, the main non-invasive method for cancer treatment, remains limited by the damages leading to the healthy tissues. A new strategy currently developed is to enhance the biological efficiency of the beam at the tumor by using heavy atoms as radio-enhancers [1]. The main work of the team is to develop new nanoagents and characterize their effects when combined to different medical radiations. In particular, the team developed an expertise in synthesizing platinum-based NPs nanoparticles using green chemistry (patent: FR1900008). Moreover combination of nanoagents with particle therapy, an alternative superior to conventional x-ray treatments, is a specificity focus of our studies. Our group already demonstrated that high-Z NPs (based on platinum but also gadolinium) strongly increase electron boost and the induction of lethal damage at molecular scale [2, 3] as well as tumor cell killing when combined to different radiations [4] [5]. More recently, the team improved the synthesis to produce multimodal nanoagents that improve radiation effect but also are able to be detected by different techniques of cellular or medical imaging.
My thesis aims in particular to study the characteristics and effects of new and more powerful NPs composed of bismuth - platinum (diameter 50 nm) and PEGylated with diamine, a platform to graft fluorescent markers at the surface - such as rhodamine (for confocal microscopy) or zirconium (for TEP). These NPs, also synthesized by the one step green chemistry, are biocompatible and not toxic in PC-3 cells neither fibroblast (up to 0.5 mM). The cell localization of NPs performed by confocal microscopy shows that the NPs are located in the cell cytoplasm not in the nucleus. This was demonstrated using newly developed 3D collagen-based cell samples that mimic tumors [6]. A major progress in my work is to show the influence of molecular oxygen (normoxic and hypoxic conditions). Other experiments performed with a higher resolution (10 nm in resolution) using X-ray tomography (ALBA synchrotron, Barcelona, Spain) shows that, in normoxic conditions, the NPs are located close to but not in mitochondria, otherwise in lysosomes.
In summary, the team continues to develop competitive treatment strategies that could in the future overcome contribute to lower side effects of radiation therapies and improve comfort of the patient, as well as to fight against radioresistant cases.
References
[1] Verry C et al. “Use of nanoparticles as radiosensitizing agents in radiotherapy: State of play”. Cancer Radiotherapie : Journal de la Societe Francaise de Radiotherapie Oncologique. (2019).
[2] Porcel et al. “Platinum nanoparticles: a promising material for future cancer therapy?” Nanotechnology 21, 85103 (2010).
[3] Schlathölter et al. “Improving proton therapy by metal-containing nanoparticles: nanoscale insights.” International Journal of Nanomedicine 11, 1549-1556 (2016).
[4] Salado-Leza, Daniela et al. “Green One-Step Synthesis of Medical Nanoagents for Advanced Radiation Therapy.” Nanotechnology, science and applications vol. 13 61-76. 7 (2020).
[5] Lux et al. “AGuIX® from bench to bedside—Transfer of an ultrasmall theranostic gadolinium-based nanoparticle to clinical medicine.” Br J Radiol (2018).
[6] Maury P, Porcel E, Mau A, et al. ‘Rapid Evaluation of Novel Therapeutic Strategies Using a 3D Collagen-Based Tissue-Like Model’. Frontiers in Bioengineering and Biotechnology (2021).