title: Improving proton therapy by metal-containing nanoparticles: nanoscale insights.
abstract: The use of nanoparticles to enhance the effect of radiation-based cancer treatments is a growing field of study and recently, even nanoparticle-induced improvement of proton therapy performance has been investigated. Aiming at a clinical implementation of this approach, it is essential to characterize the mechanisms underlying the synergistic effects of nanoparticles combined with proton irradiation. In this study, we investigated the effect of platinum- and gadolinium-based nanoparticles on the nanoscale damage induced by a proton beam of therapeutically relevant energy (150 MeV) using plasmid DNA molecular probe. Two conditions of irradiation (0.44 and 3.6 keV/μm) were considered to mimic the beam properties at the entrance and at the end of the proton track. We demonstrate that the two metal-containing nanoparticles amplify, in particular, the induction of nanosize damages (>2 nm) which are most lethal for cells. More importantly, this effect is even more pronounced at the end of the proton track. This work gives a new insight into the underlying mechanisms on the nanoscale and indicates that the addition of metal-based nanoparticles is a promising strategy not only to increase the cell killing action of fast protons, but also to improve tumor targeting.
authors.affiliation: Zernike Institute for Advanced Materials, University of Groningen, Groningen, the Netherlands.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schlathölter
authors.affiliation: Institut des Sciences Moléculaires d'Orsay (ISMO), Univ. Paris Sud, CNRS, Université Paris Saclay, Orsay Cedex, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Eustache
authors.affiliation: Institut des Sciences Moléculaires d'Orsay (ISMO), Univ. Paris Sud, CNRS, Université Paris Saclay, Orsay Cedex, France.
authors.forename: Erika
authors.initials: E
authors.lastname: Porcel
authors.affiliation: Institut des Sciences Moléculaires d'Orsay (ISMO), Univ. Paris Sud, CNRS, Université Paris Saclay, Orsay Cedex, France.
authors.forename: Daniela
authors.initials: D
authors.lastname: Salado
authors.affiliation: Institut des Sciences Moléculaires d'Orsay (ISMO), Univ. Paris Sud, CNRS, Université Paris Saclay, Orsay Cedex, France.
authors.forename: Lenka
authors.initials: L
authors.lastname: Stefancikova
authors.affiliation: Institut Lumière Matière, Villeurbanne Cedex, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Tillement
authors.affiliation: Institut Lumière Matière, Villeurbanne Cedex, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Lux
authors.affiliation: Institut Lumière Matière, Villeurbanne Cedex, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Mowat
authors.affiliation: Kernfysisch Versneller Instituut - Center for Advanced Radiation Technology (KVI-CART), University of Groningen, Groningen, the Netherlands.
authors.forename: Aleksandra K
authors.initials: AK
authors.lastname: Biegun
authors.affiliation: Kernfysisch Versneller Instituut - Center for Advanced Radiation Technology (KVI-CART), University of Groningen, Groningen, the Netherlands.
authors.forename: Marc-Jan
authors.initials: MJ
authors.lastname: van Goethem
authors.affiliation: Laboratoire de Chimie Physique, Universite Paris-Sud, Orsay Cedex, France.
authors.forename: Hynd
authors.initials: H
authors.lastname: Remita
authors.affiliation: Institut des Sciences Moléculaires d'Orsay (ISMO), Univ. Paris Sud, CNRS, Université Paris Saclay, Orsay Cedex, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Lacombe
mesh_terms: D004247:DNA / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*; D015335:Molecular Probes / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy; D010957:Plasmids / Q000737:chemistry*; D010984:Platinum / Q000737:chemistry*; D061766:Proton Therapy; D011522:Protons
chemical_list: D015335:Molecular Probes; D011522:Protons; D010984:Platinum; D004247:DNA; D005682:Gadolinium
keywords: gadolinium-based nanoparticles; nanosensitization; platinum nanoparticles; theranostics