Short communication: Nanoparticle thermotherapy and external beam radiation therapy for human prostate cancer cells

Joerg Lehmann, Arutselvan Natarajan, Gerald L Denardo, Robert Ivkov, Allan R. Foreman, Christopher Catapano, Gary Mirick, Tony Quang, Cordula Gruettner, Sally J. DeNardo

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Nanoparticle thermotherapy (NPTT) uses monoclonal antibody-linked iron oxide magnetic nanoparticles (bioprobes) for the tumor-specific thermotherapy of cancer by hysteretic heating of the magnetic component of the probes through an externally applied alternating magnetic field (AMF). The present study investigated the effect of NPTT on a human prostate cancer cell line, DU145. The concept of total heat dose (THD) as a measure for NPTT was validated on a cellular level and THD was correlated to cell death in vitro. The study, furthermore, explored the potential enhancement of the NPTT effect through added external beam radiation therapy (EBRT), because both forms of treatment have a different, and potentially complementary, mechanism of causing cell death. Methods: Using carbodiimide, 111In-DOTA-ChL6 was conjugated to dextran iron oxide 20-nm particles with polyethylene glycol COOH groups on the surface and purified as 111In-bioprobes. NPTT and EBRT were applied alone and combined to cells labeled with the bioprobes. Cell response was monitored by measuring lactate dehydrogenase (LDH), a product of cytolysis, in the medium. This distinct focus on the response to NPTT was possible, since we found in previous studies that the LDH assay was relatively insensitive to the response of cells (without bioprobes) to EBRT in the dose levels given here. Results: NPTT showed a significantly increased cell death at a total calculated heat dose of 14.51 and 29.02 J/g cells (50% and 100% AMF duty, 350 Oe, 136 kHz, 12 cycles, 20 minutes total), compared with AMF exposure in the absence of bioprobes. Adding EBRT to NPTT did not increase cell death, as measured by LDH. However, EBRT given to cells labeled with bioprobes caused significant cell death at radiation doses of 10 Gy and higher. Conclusions: In human prostate cancer cell cultures, NPTT applied as a single modality caused cell death that correlated with THD estimation; complete cell death occurred at 14.51 J/g cells. Consequently, enhancement of the NPTT effect through the addition of EBRT could not be addressed. Interestingly, EBRT induced cell death on bioprobe-labeled cells at EBRT levels that did not show cell death in the absence of bioprobes; this phenomenon is worth investigating further.

Original languageEnglish (US)
Pages (from-to)265-271
Number of pages7
JournalCancer Biotherapy and Radiopharmaceuticals
Volume23
Issue number2
DOIs
StatePublished - Apr 1 2008

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Induced Hyperthermia
Nanoparticles
Prostatic Neoplasms
Radiotherapy
Biosensing Techniques
Communication
Cell Death
Magnetic Fields
Hot Temperature
L-Lactate Dehydrogenase
Carbodiimides
Dextrans
Heating
Neoplasms
Cell Culture Techniques
Monoclonal Antibodies
Radiation

Keywords

  • Antibody
  • Irradiation
  • Nanoparticle
  • Prostate cancer
  • Thermotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

Short communication : Nanoparticle thermotherapy and external beam radiation therapy for human prostate cancer cells. / Lehmann, Joerg; Natarajan, Arutselvan; Denardo, Gerald L; Ivkov, Robert; Foreman, Allan R.; Catapano, Christopher; Mirick, Gary; Quang, Tony; Gruettner, Cordula; DeNardo, Sally J.

In: Cancer Biotherapy and Radiopharmaceuticals, Vol. 23, No. 2, 01.04.2008, p. 265-271.

Research output: Contribution to journalArticle

Lehmann, J, Natarajan, A, Denardo, GL, Ivkov, R, Foreman, AR, Catapano, C, Mirick, G, Quang, T, Gruettner, C & DeNardo, SJ 2008, 'Short communication: Nanoparticle thermotherapy and external beam radiation therapy for human prostate cancer cells', Cancer Biotherapy and Radiopharmaceuticals, vol. 23, no. 2, pp. 265-271. https://doi.org/10.1089/cbr.2007.0411
Lehmann, Joerg ; Natarajan, Arutselvan ; Denardo, Gerald L ; Ivkov, Robert ; Foreman, Allan R. ; Catapano, Christopher ; Mirick, Gary ; Quang, Tony ; Gruettner, Cordula ; DeNardo, Sally J. / Short communication : Nanoparticle thermotherapy and external beam radiation therapy for human prostate cancer cells. In: Cancer Biotherapy and Radiopharmaceuticals. 2008 ; Vol. 23, No. 2. pp. 265-271.
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abstract = "Nanoparticle thermotherapy (NPTT) uses monoclonal antibody-linked iron oxide magnetic nanoparticles (bioprobes) for the tumor-specific thermotherapy of cancer by hysteretic heating of the magnetic component of the probes through an externally applied alternating magnetic field (AMF). The present study investigated the effect of NPTT on a human prostate cancer cell line, DU145. The concept of total heat dose (THD) as a measure for NPTT was validated on a cellular level and THD was correlated to cell death in vitro. The study, furthermore, explored the potential enhancement of the NPTT effect through added external beam radiation therapy (EBRT), because both forms of treatment have a different, and potentially complementary, mechanism of causing cell death. Methods: Using carbodiimide, 111In-DOTA-ChL6 was conjugated to dextran iron oxide 20-nm particles with polyethylene glycol COOH groups on the surface and purified as 111In-bioprobes. NPTT and EBRT were applied alone and combined to cells labeled with the bioprobes. Cell response was monitored by measuring lactate dehydrogenase (LDH), a product of cytolysis, in the medium. This distinct focus on the response to NPTT was possible, since we found in previous studies that the LDH assay was relatively insensitive to the response of cells (without bioprobes) to EBRT in the dose levels given here. Results: NPTT showed a significantly increased cell death at a total calculated heat dose of 14.51 and 29.02 J/g cells (50{\%} and 100{\%} AMF duty, 350 Oe, 136 kHz, 12 cycles, 20 minutes total), compared with AMF exposure in the absence of bioprobes. Adding EBRT to NPTT did not increase cell death, as measured by LDH. However, EBRT given to cells labeled with bioprobes caused significant cell death at radiation doses of 10 Gy and higher. Conclusions: In human prostate cancer cell cultures, NPTT applied as a single modality caused cell death that correlated with THD estimation; complete cell death occurred at 14.51 J/g cells. Consequently, enhancement of the NPTT effect through the addition of EBRT could not be addressed. Interestingly, EBRT induced cell death on bioprobe-labeled cells at EBRT levels that did not show cell death in the absence of bioprobes; this phenomenon is worth investigating further.",
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AU - Catapano, Christopher

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KW - Irradiation

KW - Nanoparticle

KW - Prostate cancer

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