Photon activated therapy (PAT) using monochromatic Synchrotron x-rays and iron oxide nanoparticles in a mouse tumor model: feasibility study of PAT for the treatment of superficial malignancy

Abstract

BackgroundX-rays are known to interact with metallic nanoparticles, producing photoelectric species as radiosensitizing effects, and have been exploited in vivo mainly with gold nanoparticles. The purpose of this study was to investigate the potential of sensitizing effect of iron oxide nanoparticles for photon activated therapy.MethodsX-rays photon activated therapy (PAT) was studied by treating CT26 tumor cells and CT26 tumor-bearing mice loaded with 13-nm diameter FeO NP, and irradiating them at 7.1 keV near the Fe K-edge using synchrotron x-rays radiation. Survival of cells was determined by MTT assay, and tumor regression assay was performed for in vivo model experiment. The results of PAT treated groups were compared with x-rays alone control groups.ResultsA more significant reduction in viability and damage was observed in the FeO NP-treated irradiated cells, compared to the radiation alone group (p < 0.04). Injection of FeO NP (100 mg/kg) 30 min prior to irradiation elevated the tumor concentration of magnetite to 40 μg of Fe/g tissue, with a tumor-to-muscle ratio of 17.4. The group receiving FeO NP and radiation of 10 Gy showed 80% complete tumor regression (CTR) after 15–35 days and relapse-free survival for up to 6 months, compared to the control group, which showed growth retardation, resulting in 80% fatality. The group receiving radiation of 40 Gy showed 100% CTR in all cases irrespective of the presence of FeO NP, but CTR was achieved earlier in the PAT-treated group compared with the radiation alone group.ConclusionsAn iron oxide nanoparticle enhanced therapeutic effect with relatively low tissue concentration of iron and 10 Gy of monochromatic X-rays. Since 7.1 keV X-rays is attenuated very sharply in the tissue, FeO NP-PAT may have promise as a potent treatment option for superficial malignancies in the skin, like chest wall recurrence of breast cancer.

Enhancement of Tumor Regression by Coulomb Nanoradiator Effect in Proton Treatment of Iron-Oxide Nanoparticle-Loaded Orthotopic Rat Glioma Model: Implication of Novel Particle Induced Radiation Therapy

“…Nanoradiator effect can be obtained from either Coulomb collision with ion beam or photoelectric absorption of X-ray photon. However, ion-beam irradiation may provide much better way in the energy delivery as well as Z-value independent interaction with nanoparticles compared with X-ray photon under the normal tissue tolerance [5,15].…”

THE PHOTON CAPTURE THERAPY MODEL FOR IN VIVO AND IN VITRO STUDIES USING Au NANOCOMPOSITES WITH THE HYALURONIC ACID BASED COMPOUNDS

“…The RBE assessment is the most valuable study within the radiobiological trials and the most essential tool to reproduce the practical needs aimed at the radiotherapy schemes' development. The RBE using 10 % survival criteria for B-16 cells is 1.5, while a similar study, using the same object but with other incubation properties, was much lower -1.05 [2]. Even a higher RBE of 2.0 has been observed on the 2 Gy exposure level of mice melanoma cells (which is the fraction standard in the conventional radiotherapy schemes).…”

“…This issue can be resolved using a binary therapy method, in particular, the photon capture therapy (PCT). The metals selectively accumulated within the tumor are coupled with the Xrays' additional interaction, which finally results in the emission of the short range secondary ionization particles leading to the tumor dose enhancement [1,2]. The wide spread of the PCT method into the clinical practice is limited mostly by the lack of effective drugs and substances satisfying the method requirements: higher concentration in the tumor and precise dose escalation that could lead to the tumor growth suppression effect.…”

The study of hyaluronic acid compounds for neutron capture and photon activation therapies

“…The physical principle of photon activation therapy (PAT) consists of increasing the local release of energy (photoelectrons and Auger-electrons) that result from the photoeffect arising when the soft X-ray radiation interacts with atoms of elements with large atomic number Z [5][6][7], herewith prospects for use of gold nanoparticles in the PAT are shown in several publications [8,9]. This type of radiation therapy is most suitable for wide use in oncology practice since X-ray sources are mobile, relatively cheap and do not require special rooms with a powerful biological protection when operating and that creates conditions for PAT widespread use in the treatment of cancer patients.…”