title: A radio-frequency coupling network for heating of citrate-coated gold nanoparticles for cancer therapy: design and analysis.
abstract: Gold nanoparticles (GNPs) are nontoxic, can be functionalized with ligands, and preferentially accumulate in tumors. We have developed a 13.56-MHz RF-electromagnetic field (RF-EM) delivery system capable of generating high E-field strengths required for noninvasive, noncontact heating of GNPs. The bulk heating and specific heating rates were measured as a function of NP size and concentration. It was found that heating is both size and concentration dependent, with 5 nm particles producing a 50.6 ± 0.2 °C temperature rise in 30 s for 25 μg/mL gold (125 W input). The specific heating rate was also size and concentration dependent, with 5 nm particles producing a specific heating rate of 356 ± 78 kW/g gold at 16 μg/mL (125 W input). Furthermore, we demonstrate that cancer cells incubated with GNPs are killed when exposed to 13.56 MHz RF-EM fields. Compared to cells that were not incubated with GNPs, three out of four RF-treated groups showed a significant enhancement of cell death with GNPs (p<0.05). GNP-enhanced cell killing appears to require temperatures above 50 °C for the experimental parameters used in this study. Transmission electron micrographs show extensive vacuolization with the combination of GNPs and RF treatment.
authors.affiliation: Department of Biomedical Engineering, University of California at Davis, Davis, CA 95616, USA. dekruse@ucdavis.edu
authors.forename: Dustin E
authors.initials: DE
authors.lastname: Kruse
authors.forename: Douglas N
authors.initials: DN
authors.lastname: Stephens
authors.forename: Heather A
authors.initials: HA
authors.lastname: Lindfors
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Ingham
authors.forename: Eric E
authors.initials: EE
authors.lastname: Paoli
authors.forename: Katherine W
authors.initials: KW
authors.lastname: Ferrara
mesh_terms: D016923:Cell Death / Q000528:radiation effects; D045744:Cell Line, Tumor; D019343:Citric Acid; D004574:Electromagnetic Fields; D004867:Equipment Design; D006046:Gold / Q000737:chemistry*; D006358:Hot Temperature; D006801:Humans; D006979:Hyperthermia, Induced / Q000295:instrumentation* / Q000379:methods; D053768:Metal Nanoparticles / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D036103:Nanotechnology; D009369:Neoplasms / Q000628:therapy*; D010316:Particle Size
chemical_list: D019343:Citric Acid; D006046:Gold