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

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.