A New Generation of Ultrasmall Nanoparticles Inducing Sensitization to Irradiation and Copper Depletion to Overcome Radioresistant and Invasive Cancers
Paul Rocchi,
Delphine Brichart-Vernos,
François Lux,
Isabelle Morfin,
Laurent David,
Claire Rodriguez-Lafrasse,
Olivier Tillement
Affiliations
Paul Rocchi
Institut Lumière Matière, Université Claude Bernard Lyon 1CNRS UMR 5306, 69622 Villeurbanne, France
Delphine Brichart-Vernos
Institut Lumière Matière, Université Claude Bernard Lyon 1CNRS UMR 5306, 69622 Villeurbanne, France
François Lux
Institut Lumière Matière, Université Claude Bernard Lyon 1CNRS UMR 5306, 69622 Villeurbanne, France
Isabelle Morfin
LiPhy, Université Grenoble Alpes, CNRS, UMR UMR5588, 38401 Grenoble, France
Laurent David
Ingénierie des Matériaux Polymères, Université de Lyon, Université Claude Bernard Lyon 1, Université Jean Monet, Institut National des Sciences Appliquées de Lyon, CNRS, UMR 5223, 15, bd A. Latarjet, 69622 Villeurbanne, France
Claire Rodriguez-Lafrasse
Cellular and Molecular Radiobiology Laboratory, Lyon-Sud Medical School, UMR CNRS 5822/IP2I, Univ. Lyon, Lyon 1 University, 69921 Oullins, France
Olivier Tillement
Institut Lumière Matière, Université Claude Bernard Lyon 1CNRS UMR 5306, 69622 Villeurbanne, France
An emerging target to overcome cancer resistance to treatments is copper, which is upregulated in a wide variety of tumors and may be associated with cancer progression and metastases. The aim of this study was to develop a multimodal ultrasmall nanoparticle, CuPRiX, based on the clinical AGuIX nanoparticle made of the polysiloxane matrix on which gadolinium chelates are grafted. Such hybrid nanoparticles allow: (i) a localized depletion of copper in tumors to prevent tumor cell dissemination and metastasis formation and (ii) an increased sensitivity of the tumor to radiotherapy (RT) due to the presence of high Z gadolinium (Gd) atoms. CuPRiX nanoparticles are obtained by controlled acidification of AGuIX nanoparticles. They were evaluated in vitro on two cancer cell lines (lung and head and neck) using the scratch-wound assay and clonogenic cell survival assay. They were able to reduce cell migration and invasion and displayed radiosensitizing properties.