Therapeutic application of metallic nanoparticles combined with particle-induced x-ray emission effect

Abstract

Metallic nanoparticles (MNP) are able to release localized x-rays when activated with a high energy proton beam by the particle-induced x-ray emission (PIXE) effect. The exploitation of this phenomenon in the therapeutic irradiation of tumors has been investigated. PIXE-based x-ray emission directed at CT26 tumor cells in vitro, when administered with either gold (average diameter 2 and 13 nm) or iron (average diameter 14 nm) nanoparticles (GNP or SNP), increased with MNP solution concentration over the range of 0.1-2 mg ml(-1). With irradiation by a 45 MeV proton therapy (PT) beam, higher concentrations had a decreased cell survival fraction. An in vivo study in CT26 mouse tumor models with tumor regression assay demonstrated significant tumor dose enhancement, thought to be a result of the PIXE effect when compared to conventional PT without MNP (radiation-only group) using a 45 MeV proton beam (p < 0.02). Those receiving GNP or SNP injection doses of 300 mg kg(-1) body weight before proton beam therapy demonstrated 90% or 75% tumor volume reduction (TVR) in 20 days post-PT while the radiation-only group showed only 18% TVR and re-growth of tumor volume after 20 days. Higher complete tumor regression (CTR) was observed in 14-24 days after a single treatment of PT with an average rate of 33-65% for those receiving MNP compared with 25% for the radiation-only group. A lower bound of therapeutic effective MNP concentration range, in vivo, was estimated as 30-79 µg g(-1) tissue for both gold and iron nanoparticles. The tumor dose enhancement may compensate for an increase in entrance dose associated with conventional PT when treating large, solid tumors with a spread-out Bragg peak (SOBP) technique. The use of a combined high energy Bragg peak PT with PIXE generated by MNP, or PIXE alone, may result in new treatment options for infiltrative metastatic tumors and other diffuse inflammatory diseases.

Investigation of gold nanoparticle radiosensitization mechanisms using a free radical scavenger and protons of different energies

“…There have been a limited number of reports where relatively high energy particles (50 MeV or above) have been used to irradiate cells or tumours (Kim et al, 2012, Kim et al, 2010 …”

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

“…Recently, our laboratory found proton-impact high-Z nanoparticles produced CNR-based dose enhancement effect that led to a large therapeutic enhancement on nanoparticle-loaded mouse tumor model in either SOBP [3] or traversing Bragg peak irradiation [4]. Other groups also demonstrated the enhancement of cytotoxicity in their ion beam-impact in vitro studies on either platinum or gold-loaded cells [5,6].…”

A Monte Carlo study on dose enhancement and photon contamination production by various nanoparticles in electron mode of a medical linac

“…In other words, this increase can be a result of the particle induced X-ray emission (PIXE) effect. In this method, when metallic nanoparticles are irradiated by high energy charged particles or heavy ions, they release X-rays or gamma-rays due the particle induced X-ray emission or particle induced gamma-ray emission (PIGE) effect [23]. The consequent phenomenon is emission of Auger electrons which enhances local tumor dose, as an advantage.…”