Daniela Salado-Leza,1,2 Erika Porcel,1 Xiaomin Yang,1 Lenka tefankov,1 Marta Bolsa-Ferruz,1 Farah Savina,1 Diana Dragoe,3 Jean-Luc Guerquin-Kern,4 Ting-Di Wu,4 Ryoichi Hirayama,5 Hynd Remita,6 Sandrine Lacombe1

1Universit Paris Saclay, CNRS UMR 8214, Institut des Sciences Molculaires dOrsay, 91405 Orsay, France; 2Ctedra CONACyT, Faculty of Chemical Sciences, Autonomous University of San Luis Potos, 78210 San Luis Potos, Mexico; 3Universit Paris Saclay, CNRS UMR 8182, Institut de Chimie Molculaire et des Matriaux dOrsay, 91405 Orsay, France; 4Paris-Saclay University, Multimodal Imaging Center (UMS 2016/US 43) CNRS, INSERM, Institut Curie, 91405 Orsay, France; 5Department of Charged Particle Therapy Research, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 263-8555 Chiba, Japan; 6Universit Paris Saclay, CNRS UMR 8000, Institut de Chimie Physique, 91405 Orsay, France

Correspondence: Sandrine LacombeUniversit Paris-Saclay, CNRS UMR 8214, Institut des Sciences Molculaires dOrsay, Andr Rivire Street, Building 520, Orsay Cedex 91405, FranceTel +33 1 6915 8263Email sandrine.lacombe@universite-paris-saclay.fr

Purpose: Metal-based nanoparticles (M-NPs) have attracted great attention in nanomedicine due to their capacity to amplify and improve the tumor targeting of medical beams. However, their simple, efficient, high-yield and reproducible production remains a challenge. Currently, M-NPs are mainly synthesized by chemical methods or radiolysis using toxic reactants. The waste of time, loss of material and potential environmental hazards are major limitations.Materials and Methods: This work proposes a simple, fast and green strategy to synthesize small, non-toxic and stable NPs in water with a 100% production rate. Ionizing radiation is used to simultaneously synthesize and sterilize the containing NPs solutions. The synthesis of platinum nanoparticles (Pt NPs) coated with biocompatible poly(ethylene glycol) ligands (PEG) is presented as proof of concept. The physicochemical properties of NPs were studied by complementary specialized techniques. Their toxicity and radio-enhancing properties were evaluated in a cancerous in vitro model. Using plasmid nanoprobes, we investigated the elementary mechanisms underpinning radio-enhancement.Results and Discussion: Pt NPs showed nearly spherical-like shapes and an average hydrodynamic diameter of 9 nm. NPs are zero-valent platinum successfully coated with PEG. They were found non-toxic and have the singular property of amplifying cell killing induced by -rays (14%) and even more, the effects of carbon ions (44%) used in particle therapy. They induce nanosized-molecular damage, which is a major finding to potentially implement this protocol in treatment planning simulations.Conclusion: This new eco-friendly, fast and simple proposed method opens a new era of engineering water-soluble biocompatible NPs and boosts the development of NP-aided radiation therapies.

Keywords: platinum nanoparticles, radiolytic method, environmentally-friendly process, nanomedicine, radiotherapy

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Green One-Step Synthesis of Medical Nanoagents for Advanced Radiation | NSA - Dove Medical Press