Noninvasive radiofrequency field-induced hyperthermic cytotoxicity in human cancer cells using cetuximab-targeted gold nanoparticles

Steven A. Curley, Paul Cherukuri, Katrina Briggs, Chitta Ranjan Patra, Mark Upton, Elisa Dolson, Priyabrata Mukherjee

Research output: Contribution to journalArticle

93 Scopus citations

Abstract

Shortwave (MHz range) radiofrequency (RF) energy is nonionizing, penetrates deeply into biologic tissues with no adverse side effects, and heats gold nanoparticles efficiently. Targeted delivery of gold nanoparticles to cancer cells should result in hyperthermic cytotoxicity upon exposure to a focused, noninvasive RF field. In this report we demonstrate that gold nanoparticles conjugated with cetuximab (C225) are quickly internalized by Panc-1 (pancreatic adenocarcinoma) and Difi (colorectal adenocarcinoma) cancer cells overexpressing epidermal growth factor receptor (EGFR). Panc-1 or Difi cells treated with naked gold nanoparticles or nonspecific IgG-conjugated gold nanoparticles demonstrated minimal intracellular uptake of gold nanoparticles by transmission electron microscopy (TEM). In contrast, there were dense concentrations of cytoplasmic vesicles containing gold nanoparticles following treatment with cetuximab-conjugated gold nanoparticles. Exposure of cells to a noninvasive RF field produced nearly 100% cytotoxicity in cells treated with the cetuximab-conjugated gold nanoparticles, but significantly lower levels of cytotoxicity in the two control groups (P<0.00012). Treatment of a breast cancer cell line (CAMA-1) that does not express EGFR with cetuximab-conjugated gold nanoparticles produced no enhanced cytotoxicity following treatment in the RF field. Conjugation of cancer cell-directed targeting agents to gold nanoparticles may represent an effective and cancer-specific therapy to treat numerous types of human malignant disease using noninvasive RF hyperthermia.

Original languageEnglish (US)
Pages (from-to)313-326
Number of pages14
JournalJournal of Experimental Therapeutics and Oncology
Volume7
Issue number4
StatePublished - Dec 1 2008

Keywords

  • Radiofrequency
  • Targeted gold nanoparticles
  • Thermal cytotoxicity

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Cancer Research

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    Curley, S. A., Cherukuri, P., Briggs, K., Patra, C. R., Upton, M., Dolson, E., & Mukherjee, P. (2008). Noninvasive radiofrequency field-induced hyperthermic cytotoxicity in human cancer cells using cetuximab-targeted gold nanoparticles. Journal of Experimental Therapeutics and Oncology, 7(4), 313-326.