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

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.

AI evidence extraction

Main findings

Cetuximab-conjugated gold nanoparticles were rapidly internalized by EGFR-overexpressing Panc-1 and Difi cells, while naked or nonspecific IgG-conjugated nanoparticles showed minimal uptake. RF field exposure produced nearly 100% cytotoxicity in cells treated with cetuximab-conjugated gold nanoparticles, with significantly lower cytotoxicity in control groups (P < 0.00012). An EGFR-negative breast cancer cell line (CAMA-1) showed no enhanced cytotoxicity with cetuximab-conjugated nanoparticles after RF exposure.

Outcomes measured

• Gold nanoparticle cellular uptake/internalization (TEM)
• Cytotoxicity after RF field exposure
• EGFR-specificity of effect (comparison with EGFR-negative cell line)

Limitations

• In vitro study (cell lines); findings may not generalize to in vivo or clinical settings
• RF exposure parameters (exact frequency, SAR, duration) not specified in abstract
• Sample sizes and detailed experimental conditions not reported in abstract

Suggested hubs

• rf-hyperthermia (0.86)
  Study tests noninvasive RF-field-induced hyperthermic cytotoxicity using gold nanoparticles in cancer cell lines.

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    "study_type": "in_vitro",
    "exposure": {
        "band": "RF",
        "source": "focused, noninvasive RF field",
        "frequency_mhz": null,
        "sar_wkg": null,
        "duration": null
    },
    "population": "Human cancer cell lines (Panc-1 pancreatic adenocarcinoma; Difi colorectal adenocarcinoma; CAMA-1 breast cancer cell line)",
    "sample_size": null,
    "outcomes": [
        "Gold nanoparticle cellular uptake/internalization (TEM)",
        "Cytotoxicity after RF field exposure",
        "EGFR-specificity of effect (comparison with EGFR-negative cell line)"
    ],
    "main_findings": "Cetuximab-conjugated gold nanoparticles were rapidly internalized by EGFR-overexpressing Panc-1 and Difi cells, while naked or nonspecific IgG-conjugated nanoparticles showed minimal uptake. RF field exposure produced nearly 100% cytotoxicity in cells treated with cetuximab-conjugated gold nanoparticles, with significantly lower cytotoxicity in control groups (P < 0.00012). An EGFR-negative breast cancer cell line (CAMA-1) showed no enhanced cytotoxicity with cetuximab-conjugated nanoparticles after RF exposure.",
    "effect_direction": "harm",
    "limitations": [
        "In vitro study (cell lines); findings may not generalize to in vivo or clinical settings",
        "RF exposure parameters (exact frequency, SAR, duration) not specified in abstract",
        "Sample sizes and detailed experimental conditions not reported in abstract"
    ],
    "evidence_strength": "low",
    "confidence": 0.7399999999999999911182158029987476766109466552734375,
    "peer_reviewed_likely": "yes",
    "keywords": [
        "radiofrequency",
        "shortwave",
        "MHz range",
        "gold nanoparticles",
        "cetuximab",
        "EGFR",
        "hyperthermia",
        "cytotoxicity",
        "cancer cells",
        "Panc-1",
        "Difi",
        "CAMA-1"
    ],
    "suggested_hubs": [
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            "weight": 0.85999999999999998667732370449812151491641998291015625,
            "reason": "Study tests noninvasive RF-field-induced hyperthermic cytotoxicity using gold nanoparticles in cancer cell lines."
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