Gannon Christopher J, Cherukuri Paul, Yakobson Boris I, Cognet Laurent, Kanzius John S, Kittrell Carter, Weisman R Bruce, Pasquali Matteo, Schmidt Howard K, Smalley Richard E, Curley Steven A
Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer. 2007 Dec 15;110(12):2654-65. doi: 10.1002/cncr.23155.
Single-walled carbon nanotubes (SWNTs) have remarkable physicochemical properties that may have several medical applications. The authors have discovered a novel property of SWNTs-heat release in a radiofrequency (RF) field-that they hypothesized may be used to produce thermal cytotoxicity in malignant cells.
Functionalized, water-soluble SWNTs were exposed to a noninvasive, 13.56-megahertz RF field, and heating characteristics were measured with infrared thermography. Three human cancer cell lines were incubated with various concentrations of SWNTs and then treated in the RF field. Cytotoxicity was measured by fluorescence-activated cell sorting. Hepatic VX2 tumors in rabbits were injected with SWNTs or with control solutions and were treated in the RF field. Tumors were harvested 48 hours later to assess viability.
The RF field induced efficient heating of aqueous suspensions of SWNTs. This phenomenon was used to produce a noninvasive, selective, and SWNT concentration-dependent thermal destruction in vitro of human cancer cells that contained internalized SWNTs. Direct intratumoral injection of SWNTs in vivo followed by immediate RF field treatment was tolerated well by rabbits bearing hepatic VX2 tumors. At 48 hours, all SWNT-treated tumors demonstrated complete necrosis, whereas control tumors that were treated with RF without SWNTs remained completely viable. Tumors that were injected with SWNTs but were not treated with RF also were viable.
The current results suggested that SWNTs targeted to cancer cells may allow noninvasive RF field treatments to produce lethal thermal injury to the malignant cells. Now, the authors are developing SWNTs coupled with cancer cell-targeting agents to enhance SWNT uptake by cancer cells while limiting uptake by normal cells.
单壁碳纳米管(SWNTs)具有卓越的物理化学性质,可能有多种医学应用。作者发现了SWNTs的一种新特性——在射频(RF)场中放热,他们推测这可用于对恶性细胞产生热细胞毒性。
将功能化的水溶性SWNTs暴露于非侵入性的13.56兆赫兹射频场中,并用红外热成像测量加热特性。将三种人类癌细胞系与不同浓度的SWNTs孵育,然后在射频场中进行处理。通过荧光激活细胞分选测量细胞毒性。给兔肝VX2肿瘤注射SWNTs或对照溶液,并在射频场中进行处理。48小时后收获肿瘤以评估活力。
射频场可有效加热SWNTs的水悬浮液。利用这一现象在体外对内化了SWNTs的人类癌细胞产生了非侵入性、选择性且依赖SWNT浓度的热破坏。在体内对荷肝VX2肿瘤的兔直接瘤内注射SWNTs,随后立即进行射频场处理,兔子耐受性良好。48小时时,所有经SWNTs处理的肿瘤均显示完全坏死,而未用SWNTs仅接受射频处理的对照肿瘤仍完全存活。注射了SWNTs但未接受射频处理的肿瘤也存活。
目前的结果表明,靶向癌细胞的SWNTs可使非侵入性射频场治疗对恶性细胞产生致命的热损伤。现在,作者正在研发与癌细胞靶向剂偶联的SWNTs,以增强癌细胞对SWNTs的摄取,同时限制正常细胞的摄取。