Noninvasive radiofrequency field destruction of pancreatic adenocarcinoma xenografts treated with targeted gold nanoparticles

Evan Glazer, Cihui Zhu, Katheryn L. Massey, C. Shea Thompson, Warna D. Kaluarachchi, Amir N. Hamir, Steven A. Curley

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

Purpose: Pancreatic carcinoma is one of the deadliest cancers with few effective treatments. Gold nanoparticles (AuNP) are potentially therapeutic because of the safety demonstrated thus far and their physiochemical characteristics. We used the astounding heating rates of AuNPs in nonionizing radiofrequency (RF) radiation to investigate human pancreatic xenograft destruction in a murine model. Experimental Design: Weekly, Panc-1 and Capan-1 human pancreatic carcinoma xenografts in immunocompromised mice were exposed to an RF field 36 hours after treatment (intraperitoneal) with cetuximab- or PAM4 antibody-conjugated AuNPs, respectively. Tumor sizes were measured weekly, whereas necrosis and cleaved caspase-3 were investigated with hematoxylin-eosin staining and immunofluorescence, respectively. In addition, AuNP internalization and cytotoxicity were investigated in vitro with confocal microscopy and flow cytometry, respectively. Results: Panc-1 cells demonstrated increased apoptosis with decreased viability after treatment with cetuximab-conjugated AuNPs and RF field exposure (P = 0.00005). Differences in xenograft volumes were observed within 2 weeks of initiating therapy. Cetuximab- and PAM4-conjugated AuNPs demonstrated RF field-induced destruction of Panc-1 and Capan-1 pancreatic carcinoma xenografts after 6 weeks of weekly treatment (P = 0.004 and P = 0.035, respectively). There was no evidence of injury to murine organs. Cleaved caspase-3 and necrosis were both increased in treated tumors. Conclusions: This study demonstrates a potentially novel cancer therapy by noninvasively inducing intracellular hyperthermia with targeted AuNPs in an RF field. While the therapy is dependent on the specificity of the targeting antibody, normal tissues were without toxicity despite systemic therapy and whole-body RF field exposure.

Original languageEnglish (US)
Pages (from-to)5712-5721
Number of pages10
JournalClinical Cancer Research
Volume16
Issue number23
DOIs
StatePublished - Dec 1 2010

Fingerprint

Heterografts
Gold
Nanoparticles
Adenocarcinoma
Therapeutics
Caspase 3
Neoplasms
Necrosis
Nonionizing Radiation
Antibody Specificity
Hematoxylin
Eosine Yellowish-(YS)
Confocal Microscopy
Heating
Fluorescent Antibody Technique
Flow Cytometry
Research Design
Fever
Apoptosis
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Noninvasive radiofrequency field destruction of pancreatic adenocarcinoma xenografts treated with targeted gold nanoparticles. / Glazer, Evan; Zhu, Cihui; Massey, Katheryn L.; Thompson, C. Shea; Kaluarachchi, Warna D.; Hamir, Amir N.; Curley, Steven A.

In: Clinical Cancer Research, Vol. 16, No. 23, 01.12.2010, p. 5712-5721.

Research output: Contribution to journalArticle

Glazer, Evan ; Zhu, Cihui ; Massey, Katheryn L. ; Thompson, C. Shea ; Kaluarachchi, Warna D. ; Hamir, Amir N. ; Curley, Steven A. / Noninvasive radiofrequency field destruction of pancreatic adenocarcinoma xenografts treated with targeted gold nanoparticles. In: Clinical Cancer Research. 2010 ; Vol. 16, No. 23. pp. 5712-5721.
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