多壁式扶手型碳纳米管结构示意图。图片来自维基共享资源。
来自美国维克森林大学浸礼会医学中心(Wake Forest University Baptist Medical Center)的研究人员再次证实将多壁式碳纳米管(multiwalled carbon nanotubes, MWCNTs)注射进肿瘤中并且通过激光快速照射30秒时间对这些肿瘤加热就能够杀死它们。
2009年,他们利用同样方法发表第一篇涉及肾脏肿瘤的研究论文,而如今他们利用这种技术瞄准乳腺肿瘤,特别是起始肿瘤发生的癌干细胞。这些干细胞很难杀死,因为它们并不经常发生分裂,而很多抗癌策略旨在杀死那些经常发生分裂的细胞。
这一研究发现在线发表在Biomaterials期刊上。该研究通讯作者Suzy V. Torti教授说,乳腺癌干细胞往往抵抗药物和放射治疗,因此靶向这些特殊的细胞引起整个科学界的兴趣。
Torti解释道,“它们很顽强。它们是不经常发生分裂的细胞。它们只是静息地呆在那里,但是当它们接收到某些人们现在仍然没有很好理解的激发信号时,它们被认为能够迁移到其他位点和开始转移到其他地方。就临床治疗包括在乳腺癌在内的癌症而言,基于加热的癌症治疗代表着一种大有希望的方法。”
研究人员使用模式小鼠开展研究,将由碳构成的非常小的纳米管注射进含有乳腺癌干细胞的肿瘤中。Torti说,就纳米管本身而言,它们没有任何抗肿瘤性质,但是如果它们暴露在激光产生的近红外线照射下,它们开始振动并产生热量。她说,这种组合能够在肿瘤中产生一个非常热的局部区域。研究小组利用这种方法能够阻止主要由乳腺癌干细胞组成的肿瘤进行生长。这一发现提示着纳米管介导的热处理能够消灭构成肿瘤大部分的已分化的癌细胞,同时也能够消灭促进肿瘤生长和复发的癌干细胞。
Torti说,“为了真正地治疗一种癌症,人们必须除去整个肿瘤,包括能够导致肿瘤转移的一小群癌干细胞。不过仍有需要进行更多的研究。我们正考虑进行5到10年的研发。但是这项研究证实这种努力可能是值得的,因为它给我们指明探索癌症治疗的方向。” (生物谷:towersimper编译)
doi:10.1016/j.biomaterials.2011.12.052
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The resistance of breast cancer stem cells to conventional hyperthermia and their sensitivity to nanoparticle-mediated photothermal therapy
Andrew R. Burke, Ravi N. Singh, David L. Carroll, James C.S. Wood, Ralph B. D’Agostino Jr., f, Pulickel M. Ajayan, Frank M. Torti, Suzy V. Torti
Breast tumors contain a small population of tumor initiating stem-like cells, termed breast cancer stem cells (BCSCs). These cells, which are refractory to chemotherapy and radiotherapy, are thought to persist following treatment and drive tumor recurrence. We examined whether BCSCs are similarly resistant to hyperthermic therapy, and whether nanoparticles could be used to overcome this resistance. Using a model of triple-negative breast cancer stem cells, we show that BCSCs are markedly resistant to traditional hyperthermia and become enriched in the surviving cell population following treatment. In contrast, BCSCs are sensitive to nanotube-mediated thermal treatment and lose their long-term proliferative capacity after nanotube-mediated thermal therapy. Moreover, use of this therapy in vivo promotes complete tumor regression and long-term survival of mice bearing cancer stem cell-driven breast tumors. Mechanistically, nanotube thermal therapy promotes rapid membrane permeabilization and necrosis of BCSCs. These data suggest that nanotube-mediated thermal treatment can simultaneously eliminate both the differentiated cells that constitute the bulk of a tumor and the BCSCs that drive tumor growth and recurrence.