Study type: Medical/biological study (experimental study)

Carbon nanotube-enhanced thermal destruction of cancer cells in a noninvasive radiofrequency field med./bio.

By: Gannon CJ, Cherukuri P, Yakobson BI, Cognet L, Kanzius JS, Kittrell C, Weisman RB, Pasquali M, Schmidt HK, Smalley RE, Curley SA
Published in: Cancer 2007; 110 (12): 2654-2665
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Aim of study (acc. to author)

The authors combined a radiofrequency field-generating system with single-walled carbon nanotubes (SWNTs), which act efficiently to convert radiofrequency irradiation into heat, and they investigated the effect of such exposure on three different human cancer cell lines and on an in vivo animal model.

Background/further details

Hepatic VX2 tumors were injected in rabbits with single-walled carbon nanotubes or with control solutions and were treated in the radiofrequency field. Tumors were harvested 48 hours later to assess viability.

Endpoint

Exposure

Exposure Parameters
Exposure 1: 13.56 MHz
thermal effect of RF fields on functionalised SWNTs
Exposure 2: 13.56 MHz
Exposure duration: continuous for 1 or 2 min
Exposure 3: 13.56 MHz
Exposure duration: continuous for 2 min
tumour-bearing animal model in vivo

Exposure 1

Main characteristics
Frequency 13.56 MHz
Type
Additional info thermal effect of RF fields on functionalised SWNTs
Exposure setup
Exposure source
  • RF generator
Chamber The RF generator was connected to a high Q coupling system consisting of a transmitting (Tx) and a receiving (Rx) head with adjustable distance mounted on a swivel bracket, allowing the RF field to be oriented horizontally or vertically. A focused electromagnetic field was produced with a useful diameter of 30 cm and with a peak intensity at 7 cm from the central axis of the Tx and Rx heads.
Setup Five different concentrations of functionalized single-walled carbon nanotubes (SWNTs, 5 mg/l, 50 mg/l, 125 mg/l, 250 mg/l, and 500 mg/l) were diluted in deionised water and placed in a 1.5-ml circular quartz cuvette located between the Tx and Rx heads (7.5 cm apart). The samples were located at the mid plane of the working volume.
Additional info Temperature in the SWNT solutions, in solutions without SWNTs, and in water alone were measured continuously before, during, and for 2 minutes after the RF field activation.
Parameters
Measurand Value Type Method Mass Remarks
electric field strength 10.1 kV/m maximum estimated - -
electric field strength 12.4 kV/m maximum estimated - -
electric field strength 14.3 kV/m maximum estimated - -
electric field strength 16 kV/m maximum estimated - -
Additional parameter details

Output powers used yielded the indicated maximum estimated electric field strengths at 2.5 cm from the Tx head.

Measurement and calculation details

The field strength was measured in a Faraday-shielded room at low output power using an isotropic field monitor and probe.

Exposure 2

Main characteristics
Frequency 13.56 MHz
Type
Exposure duration continuous for 1 or 2 min
Additional info human cancer cells in vitro
Exposure setup
Exposure source
Setup Cells were placed individually on a Teflon holder between the Tx and Rx heads that were oriented vertically and 7.5 cm apart. Media containing various concentrations of SWNTs, solution without SWNTs, or media alone were added to the cells grown to near confluence.
Parameters
Measurand Value Type Method Mass Remarks
electric field strength 14.3 kV/m maximum estimated - -

Exposure 3

Main characteristics
Frequency 13.56 MHz
Type
Exposure duration continuous for 2 min
Additional info tumour-bearing animal model in vivo
Exposure setup
Exposure source
Setup Animals were placed individually on a platform between the Tx and Rx heads that were oriented vertically and 10 cm apart. Each animal was positioned so the hepatic tumour was located at the mid plane of the working volume.
Additional info An intrahepatic tumour introduced in the rabbits was injected directly with either a solution of SWNTs (500 mg/l) or with a control solution (no SWNTs). A control group obtained an injection of SWNTs but was not treated with RF. A final control group received RF exposure without injection of SWNTs or control solution.
Parameters
Measurand Value Type Method Mass Remarks
electric field strength 12.4 kV/m maximum estimated - -

Exposed system:

Methods Endpoint/measurement parameters/methodology

Investigated system:
Investigated organ system:
Time of investigation:
  • after exposure

Main outcome of study (acc. to author)

The radiofrequency field induced efficient heating of aqueous suspensions of single-walled carbon nanotubes (cf. field 1). This phenomenon was used to produce a non-invasive, selective, and carbon nanotube concentration-dependent thermal destruction in vitro of cancer cell lines that contained internalized single-walled carbon nanotubes.
Direct intra-tumoral injection of the carbon nanotubes in vivo followed by immediate radiofrequency field treatment was tolerated well by the animals bearing hepatic VX2 tumors. At 48 hours, all single-walled carbon nanotubes-treated tumors demonstrated complete necrosis, whereas control tumors that were treated with radiofrequency but without the carbon nanotubes remained completely viable. Tumors that were injected with the carbon nanotubes but were not treated with radiofrequency also were viable.
The data suggest that single-walled carbon nanotubes targeted to cancer cells may allow non-invasive radiofrequency field treatments to produce lethal thermal injury to the malignant cells. Now, the authors are developing single-walled carbon nanotubes coupled with cancer cell-targeting agents to enhance single-walled carbon nanotubes uptake by cancer cells while limiting uptake by normal cells.

Study character: