Noninvasive radiofrequency ablation of cancer targeted by gold nanoparticles.

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.

[1]  Kenneth Hess,et al.  Recurrence and Outcomes Following Hepatic Resection, Radiofrequency Ablation, and Combined Resection/Ablation for Colorectal Liver Metastases , 2004, Annals of surgery.

[2]  Y. Fong,et al.  Surgical therapy of liver metastases. , 2007, Seminars in oncology.

[3]  J. Hainfeld,et al.  The use of gold nanoparticles to enhance radiotherapy in mice. , 2004, Physics in medicine and biology.

[4]  John Wong,et al.  Learning Curve for Radiofrequency Ablation of Liver Tumors: Prospective Analysis of Initial 100 Patients in a Tertiary Institution , 2004, Annals of surgery.

[5]  S L Dawson,et al.  Tissue ablation with radiofrequency: effect of probe size, gauge, duration, and temperature on lesion volume. , 1995, Academic radiology.

[6]  S. Kakar,et al.  Epidermal growth factor receptor expression and gene copy number in fibrolamellar hepatocellular carcinoma. , 2006, Human pathology.

[7]  De-gang Fu,et al.  Effect of surface chemistry modification of functional gold nanoparticles on the drug accumulation of cancer cells. , 2008, Journal of biomedical materials research. Part A.

[8]  Guy Marchal,et al.  Local Recurrence After Hepatic Radiofrequency Coagulation: Multivariate Meta-Analysis and Review of Contributing Factors , 2005, Annals of surgery.

[9]  Chunxin Zhang,et al.  Significant effect of size on the in vivo biodistribution of gold composite nanodevices in mouse tumor models. , 2007, Nanomedicine : nanotechnology, biology, and medicine.

[10]  C. Wilcox,et al.  Antitumor and anticarcinogenic actions of Cpd 5: a new class of protein phosphatase inhibitor. , 2003, Carcinogenesis.

[11]  Matteo Pasquali,et al.  Carbon nanotube‐enhanced thermal destruction of cancer cells in a noninvasive radiofrequency field , 2007, Cancer.

[12]  D. Geller,et al.  Radiofrequency Ablation of Hepatocellular Carcinoma , 2009 .

[13]  Steven A Curley,et al.  Radiofrequency ablation , 2004, Cancer.

[14]  J. McGahan,et al.  Hepatic ablation using radiofrequency electrocautery. , 1990, Investigative radiology.

[15]  L. Buscarini,et al.  Thermal Lesions Induced by 480 KHz Localized Current Field in Guinea Pig and Pig Liver , 1990, Tumori.

[16]  H. Hirai 4. Hepatocellular Cancer , 1987 .

[17]  E F Halpern,et al.  Percutaneous radio-frequency ablation of hepatic metastases from colorectal cancer: long-term results in 117 patients. , 2001, Radiology.

[18]  P. Couvreur,et al.  Nanoparticles in cancer therapy and diagnosis. , 2002, Advanced drug delivery reviews.

[19]  N. Kotov,et al.  Gold nanoparticles enhance the anti-leukemia action of a 6-mercaptopurine chemotherapeutic agent. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[20]  Kwon-Ha Yoon,et al.  Colloidal Gold Nanoparticles as a Blood-Pool Contrast Agent for X-ray Computed Tomography in Mice , 2007, Investigative radiology.

[21]  John C. Bischof,et al.  Enhancement of tumor thermal therapy using gold nanoparticle–assisted tumor necrosis factor-α delivery , 2006, Molecular Cancer Therapeutics.

[22]  C. Murphy,et al.  Gold nanoparticles are taken up by human cells but do not cause acute cytotoxicity. , 2005, Small.

[23]  Lawrence Tamarkin,et al.  Colloidal Gold: A Novel Nanoparticle Vector for Tumor Directed Drug Delivery , 2004, Drug delivery.

[24]  M. Kim,et al.  Glypican‐3 is overexpressed in human hepatocellular carcinoma , 2003, Cancer science.

[25]  L. Ellis,et al.  Radiofrequency Ablation of Unresectable Primary and Metastatic Hepatic Malignancies: Results in 123 Patients , 1999 .

[26]  Peter Eaton,et al.  Gold nanoparticles for the development of clinical diagnosis methods , 2008, Analytical and bioanalytical chemistry.

[27]  S. Rogers,et al.  Laparoscopic radiofrequency ablation of primary and metastaticliver tumors , 2000, Surgical Endoscopy.

[28]  É. Duguet,et al.  Magnetic nanoparticle design for medical diagnosis and therapy , 2004 .