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. 2008 Aug;144(2):125-32.
doi: 10.1016/j.surg.2008.03.036.

Noninvasive radiofrequency ablation of cancer targeted by gold nanoparticles

Affiliations

Noninvasive radiofrequency ablation of cancer targeted by gold nanoparticles

Jon Cardinal et al. Surgery. 2008 Aug.

Abstract

Introduction: Current radiofrequency ablation (RFA) techniques require invasive needle placement and are limited by accuracy of targeting. The purpose of this study was to test a novel non invasive radiowave machine that uses RF energy to thermally destroy tissue. Gold nanoparticles were designed and produced to facilitate tissue heating by the radiowaves.

Methods: A solid state radiowave machine consisting of a power generator and transmitting/receiving couplers which transmit radiowaves at 13.56 MHz was used. Gold nanoparticles were produced by citrate reduction and exposed to the RF field either in solutions testing or after incubation with HepG2 cells. A rat hepatoma model using JM-1 cells and Fisher rats was employed using direct injection of nanoparticles into the tumor to focus the radiowaves for select heating. Temperatures were measured using a fiber-optic thermometer for real-time data.

Results: Solutions containing gold nanoparticles heated in a time- and power-dependent manner. HepG2 liver cancer cells cultured in the presence of gold nanoparticles achieved adequate heating to cause cell death upon exposure to the RF field with no cytotoxicity attributable to the gold nanoparticles themselves. In vivo rat exposures at 35 W using direct gold nanoparticle injections resulted in significant temperature increases and thermal injury at subcutaneous injection sites as compared to vehicle (water) injected controls.

Discussion: These data show that non invasive radiowave thermal ablation of cancer cells is feasible when facilitated by gold nanoparticles. Future studies will focus on tumor selective targeting of nanoparticles for in vivo tumor destruction.

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Figures

Figure 1
Figure 1
Equipment and set up of novel radiofrequency field generator. The RF field generator consists of a power source connected to transmitting and receiving heads. Solutions, cells in culture, or animals can be placed into the center of the field for exposure.
Figure 2
Figure 2
Au-NP solutions are heated selectively and efficiently in RF field. A. Solutions of Au-NP (squares) or water (diamonds) were exposed to the RF field at 50W and temperatures were measured over time. Results reported are averages of three separate experiments. B. Solutions of Au-NP (black) or water (white) were exposed to the RF field at 10, 50, or 100W and temperatures were measured after 3 minutes. Results reported are the averages of three separate experiments.
Figure 3
Figure 3
In vitro cell culture demonstrates effective heating and cell death with Au-NP treated cells in the RF field. A. Temperature of HepG2 cells exposed to 35W in the RF field in the presence (squares) or absence (diamonds) of Au-NP over a timecourse. Results reported are the average of three separate experiments. B. Percent cell death as assessed by LDH assay of HepG2 cells exposed to 35W in the RF field for 3, 5 or 7 minutes in the presence (black) or absence (white) of Au-NP. Results reported are the average of three separate experiments. C. Western blot for β-actin on the supernatants of HepG2 cells exposed to 35W in the RF field in the presence or absence of Au-NP for 5 or 7 minutes.
Figure 4
Figure 4
Au-NP injection focuses the RF field for effective tissue ablation in vivo. A. Male Buffalo rats were injected subcutaneously in the shoulder with 0.5mL of either sterile water (white) or Au-NP (black) and were placed in the RF field at 35W for a duration of 7 minutes. Temperatures at the injection site were measured each minute. Results are reported as the change in temperature from baseline at the site of injection. B. Histologic assessment of subcutaneous injection site in sterile water injected animals reveals generally normal tissue architecture with no significant signs of inflammation. C. Tissue from Au-NP injected animals treated in the RF field demonstrates loss of tissue architecture and infiltration of inflammatory cells.
Figure 5
Figure 5
Effect of RF field exposure on subcutaneous JM-1 hepatoma nodules. The photomicrograph compares RF exposure following injection of gold nanoparticles (A, B) or sterile water (C, D) into tumors. A. Low power photomicrograph shows relatively uniform cellular appearance of tumor with surrounding soft tissue present in upper portion of image (H&E, 100x). B. Closer view shows areas of tumor cell disaggregation, cell fragments, hyperchromatic nuclei and retracted cytoplasm. These features are compatible with thermal injury (H&E, 600x). C. Overview of control tumor shows area of confluent necrosis in the lower left-hand portion of the photograph with a sheet of viable tumor cells comprising the remainder of the image (H&E x100). D. Interface of viable tumor area (upper right) and necrotic region (lower left) (H&E x600).

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