Therapeutic application of metallic nanoparticles combined with particle-induced x-ray emission effect.
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.
Kim
Jong-Ki
JK
Biomedical Engineering and Radiology, School of Medicine, Catholic University of Daegu, Daegu, Korea. jkkim@cu.ac.kr
Seo
Seung-Jun
SJ
Kim
Ki-Hong
KH
Kim
Tae-Jeong
TJ
Chung
Myung-Hwan
MH
Kim
Kye-Ryung
KR
Yang
Tae-Keun
TK
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
D006046:Gold; D007501:Iron