title: 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.
authors.affiliation: Biomedical Engineering and Radiology, School of Medicine, Catholic University of Daegu, Daegu, Korea. jkkim@cu.ac.kr
authors.forename: Jong-Ki
authors.initials: JK
authors.lastname: Kim
authors.forename: Seung-Jun
authors.initials: SJ
authors.lastname: Seo
authors.forename: Ki-Hong
authors.initials: KH
authors.lastname: Kim
authors.forename: Tae-Jeong
authors.initials: TJ
authors.lastname: Kim
authors.forename: Myung-Hwan
authors.initials: MH
authors.lastname: Chung
authors.forename: Kye-Ryung
authors.initials: KR
authors.lastname: Kim
authors.forename: Tae-Keun
authors.initials: TK
authors.lastname: Yang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D006046:Gold / Q000627:therapeutic use*; D006801:Humans; D007501:Iron / Q000627:therapeutic use*; D053768:Metal Nanoparticles / Q000627:therapeutic use*; D051379:Mice; D009369:Neoplasms / Q000532:radiotherapy*; D061766:Proton Therapy
chemical_list: D006046:Gold; D007501:Iron