Zinc-Doped Iron Oxide Nanoparticles as a Proton-Activatable Agent for Dose Range Verification in Proton Therapy. 2023

Marta Ibáñez-Moragues, and Irene Fernández-Barahona, and Rocío Santacruz, and Marta Oteo, and Víctor M Luján-Rodríguez, and María Muñoz-Hernando, and Natalia Magro, and Juan I Lagares, and Eduardo Romero, and Samuel España, and Andrea Espinosa-Rodríguez, and Miguel García-Díez, and Víctor Martínez-Nouvilas, and Víctor Sánchez-Tembleque, and José Manuel Udías, and Víctor Valladolid-Onecha, and Miguel Á Martín-Rey, and Edilia I Almeida-Cordon, and Sílvia Viñals I Onsès, and José Manuel Pérez, and Luis Mario Fraile, and Fernando Herranz, and Miguel Ángel Morcillo
Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas CIEMAT, Medical Applications of Ionizing Radiation Unit, 28040 Madrid, Spain.

Proton therapy allows the treatment of specific areas and avoids the surrounding tissues. However, this technique has uncertainties in terms of the distal dose fall-off. A promising approach to studying the proton range is the use of nanoparticles as proton-activatable agents that produce detectable signals. For this, we developed an iron oxide nanoparticle doped with Zn (IONP@Zn-cit) with a hydrodynamic size of 10 nm and stability in serum. Cytotoxicity, defined as half of the surveillance, was 100 μg Zn/mL in the U251 cell line. The effect on clonogenic cell death was tested after X-ray irradiation, which suggested a radioprotective effect of these nanoparticles at low concentrations (1-10 μg Zn/mL). To evaluate the production of positron emitters and prompt-gamma signals, IONP@Zn-cit was irradiated with protons, obtaining prompt-gamma signals at the lowest measured concentration (10 mg Zn/mL). Finally, 67Ga-IONP@Zn-cit showed accumulation in the liver and spleen and an accumulation in the tumor tissue of 0.95% ID/g in a mouse model of U251 cells. These results suggest the possibility of using Zn nanoparticles as proton-activatable agents to verify the range by prompt gamma detection and face the challenges of prompt gamma detection in a specific biological situation, opening different avenues to go forward in this field.

UI MeSH Term Description Entries
D011522 Protons Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. Hydrogen Ions,Hydrogen Ion,Ion, Hydrogen,Ions, Hydrogen,Proton
D000082662 Magnetic Iron Oxide Nanoparticles Synthesized nanoparticles related to iron oxide crystalline structures with magnetic properties useful for biomedical applications. Examples include hematite, magnetite and maghemite nanoparticles. Hematite Nanoparticles,IONPs,Iron Oxide Nanoparticles,Maghemite Nanoparticles,Magnetic IONPs,Magnetic Iron Nanoparticles,SPIONs,Superparamagnetic Iron Nanoparticles,Superparamagnetic Iron Oxide Nanoparticles,Hematite Nanoparticle,IONP, Magnetic,IONPs, Magnetic,Iron Nanoparticle, Magnetic,Iron Nanoparticle, Superparamagnetic,Iron Oxide Nanoparticle,Maghemite Nanoparticle,Magnetic IONP,Magnetic Iron Nanoparticle,Nanoparticle, Hematite,Nanoparticle, Iron Oxide,Nanoparticle, Maghemite,Nanoparticle, Magnetic Iron,Nanoparticle, Superparamagnetic Iron,Nanoparticles, Hematite,Nanoparticles, Iron Oxide,Nanoparticles, Maghemite,Nanoparticles, Magnetic Iron,Nanoparticles, Superparamagnetic Iron,Superparamagnetic Iron Nanoparticle
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015032 Zinc A metallic element of atomic number 30 and atomic weight 65.38. It is a necessary trace element in the diet, forming an essential part of many enzymes, and playing an important role in protein synthesis and in cell division. Zinc deficiency is associated with ANEMIA, short stature, HYPOGONADISM, impaired WOUND HEALING, and geophagia. It is known by the symbol Zn.
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D053758 Nanoparticles Nanometer-sized particles that are nanoscale in three dimensions. They include nanocrystaline materials; NANOCAPSULES; METAL NANOPARTICLES; DENDRIMERS, and QUANTUM DOTS. The uses of nanoparticles include DRUG DELIVERY SYSTEMS and cancer targeting and imaging. Nanocrystalline Materials,Nanocrystals,Material, Nanocrystalline,Materials, Nanocrystalline,Nanocrystal,Nanocrystalline Material,Nanoparticle
D061766 Proton Therapy The use of an external beam of PROTONS as radiotherapy. Proton Beam Radiation Therapy,Proton Beam Therapy,Proton Beam Therapies,Proton Therapies,Therapies, Proton,Therapies, Proton Beam,Therapy, Proton,Therapy, Proton Beam

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