研究のタイプ: 医学/生物学の研究 (experimental study)

[非侵襲的無線周波電磁界中でのがん細胞の熱的破壊のカーボンナノチューブによる増強] med./bio.

Carbon nanotube-enhanced thermal destruction of cancer cells in a noninvasive radiofrequency field

掲載誌: Cancer 2007; 110 (12): 2654-2665

この研究は、単層カーボンナノチューブ(SWNT)が高周波RF電磁界中で熱を放出するという特性をがん治療に応用するために基礎的実験を行った。この機能を持った水溶性SWNTに、非侵襲的レベルの13.56 MHz RF電磁界ばく露を与え、その加熱特性を赤外線サーモグラフィで測定した。次に、3つのヒトがん細胞株をさまざまな濃度のSWNTとともにインキュベートした後、RF電磁界ばく露を与えた。細胞毒性を蛍光活性化細胞ソーティングにより評価した。その次に、ウサギの肝VX2腫瘍にSWNTまたは対照溶液を注入し、RF電磁界ばく露を与える実験を行った。48時間後に腫瘍を摘出して生存率を評価した。その結果、RF電磁界は、SWNTの水性懸濁液の効率的加熱を引き起こした;この現象は、SWNTを取り込ませたヒトがん細胞を、インビトロで、非侵襲的、選択的、かつSWNT濃度依存的に熱破壊するために活用された;インビボでSWNTを腫瘍注射した直後に行われたRF電磁界処置に、肝VX2腫瘍を担ったウサギは十分に耐えた;48時間で、すべてのSWNT処置腫瘍は完全な壊死を示したが、SWNTなしでRF処置された対照腫瘍は完全に生存可能であった;また、SWNTは注入されたがRF処置なしの腫瘍も生存可能であった、と報告している。

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研究目的(著者による)

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.

詳細情報

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.

影響評価項目

ばく露

ばく露 パラメータ
ばく露1: 13.56 MHz
thermal effect of RF fields on functionalised SWNTs
ばく露2: 13.56 MHz
ばく露時間: continuous for 1 or 2 min
human cancer cells in vitro
ばく露3: 13.56 MHz
ばく露時間: continuous for 2 min
tumour-bearing animal model in vivo

ばく露1

主たる特性
周波数 13.56 MHz
タイプ
  • electromagnetic field
Additional information thermal effect of RF fields on functionalised SWNTs
ばく露装置
ばく露の発生源/構造
  • RF generator
チャンバの詳細 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.
ばく露装置の詳細 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 information 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.
パラメータ
測定量 種別 Method Mass 備考
電界強度 10.1 kV/m maximum 推定値 - -
電界強度 12.4 kV/m maximum 推定値 - -
電界強度 14.3 kV/m maximum 推定値 - -
電界強度 16 kV/m maximum 推定値 - -

ばく露2

主たる特性
周波数 13.56 MHz
タイプ
  • electromagnetic field
ばく露時間 continuous for 1 or 2 min
Additional information human cancer cells in vitro
ばく露装置
ばく露の発生源/構造
  • E1と同じ装置
ばく露装置の詳細 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.
パラメータ
測定量 種別 Method Mass 備考
電界強度 14.3 kV/m maximum 推定値 - -

ばく露3

主たる特性
周波数 13.56 MHz
タイプ
  • electromagnetic field
ばく露時間 continuous for 2 min
Additional information tumour-bearing animal model in vivo
ばく露装置
ばく露の発生源/構造
  • E1と同じ装置
ばく露装置の詳細 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 information 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.
パラメータ
測定量 種別 Method Mass 備考
電界強度 12.4 kV/m maximum 推定値 - -

ばく露を受けた生物:

方法 影響評価項目/測定パラメータ/方法

研究対象とした生物試料:
研究対象とした臓器系:
  • liver
調査の時期:
  • ばく露後

研究の主なアウトカム(著者による)

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.

研究の種別: