在小鼠中的一項(xiàng)新的研究報(bào)告說,，將金納米粒子注射到乳腺腫瘤之中可使該腫瘤細(xì)胞對放療更為敏感,。 金納米殼技術(shù)目前正在進(jìn)行臨床試驗(yàn),，它可能會給罹患難治性乳腺癌患者提供所需的殺滅腫瘤細(xì)胞的額外的推動力,。
人們抗擊乳腺癌所遭遇的最大的障礙之一是該腫瘤中存在著一小群的腫瘤干細(xì)胞,，它們比主體的腫瘤細(xì)胞對放療和化療有著更大的抵抗力,；治療后腫瘤的再生常常歸咎于這些腫瘤干細(xì)胞。 為尋求殺滅盡可能多的癌癥細(xì)胞,，科學(xué)家們發(fā)明了伴隨放療和其它常規(guī)療法的新技術(shù),，其中包括熱療，即讓身體組織接觸高達(dá)45攝氏度（113華氏度）的高溫,。 以往的研究顯示,，灼熱的溫度可損傷并殺死癌癥細(xì)胞，并可使癌癥干細(xì)胞對放療更為敏感,，同時(shí)對正常組織的損傷也是最小的,。 然而，在過去的幾年中,，對乳腺癌實(shí)行熱療已大體上被人拋棄,，因?yàn)榻o腫瘤快速加溫但又不灼傷周邊組織是困難的。 為了解決這一問題，Rachel Atkinson及其同事設(shè)計(jì)制造了金納米粒子來給腫瘤干細(xì)胞加溫,，并使它們對放療變得更為敏感,。 他們證明，施行使用金納米粒子的熱療可有效地壓制小鼠乳腺癌模型中的癌癥干細(xì)胞,。
黃金是納米球殼（即極小的球狀硅石塊）的理想性的涂層,，因?yàn)樗谏锝M織中要比其它金屬的毒性小。在該試驗(yàn)中,，人們向小鼠的腫瘤中直接注射了一劑金納米球殼,。這些金納米球殼會滲漏到血管之外及在腫瘤內(nèi)聚集，并在被激光激活的時(shí)候造成局部加溫,。這一由納米球殼所誘導(dǎo)的加溫阻止了腫瘤細(xì)胞對由放療所導(dǎo)致的雙股DNA斷裂的修復(fù),，因而增加了它們對放療的敏感性。在注射了金納米球殼一天之后,，小鼠接受了單一劑量的放療或單一劑量的放療及20分鐘的熱療,。在治療2天之后，那些僅僅接受放療的小鼠的癌癥細(xì)胞分裂速度更快并會比那些沒有接受治療的小鼠更為活躍地形成更多的腫瘤,。另一方面,，那些接受放療加熱療的小鼠，其癌癥細(xì)胞的萌生速度較慢,，形成的腫瘤較少,，表明熱療阻止了癌癥干細(xì)胞的生長并可能改變了其迅速生長的特性。研究人員接著又做了更進(jìn)一步的試驗(yàn)：對在小鼠體內(nèi)繁殖的人的乳腺腫瘤細(xì)胞重復(fù)了以上的試驗(yàn),。他們再一次看到,，由納米球殼誘導(dǎo)的加溫效應(yīng)使得人的乳腺腫瘤干細(xì)胞對放療變得更為敏感。（生物谷Bioon.com）
生物谷推薦英文摘要：
Sci Transl Med DOI: 10.1126/scitranslmed.3001447
Thermal Enhancement with Optically Activated Gold Nanoshells Sensitizes Breast Cancer Stem Cells to Radiation Therapy
Rachel L. Atkinson1, Mei Zhang2, Parmeswaran Diagaradjane3, Sirisha Peddibhotla2, Alejandro Contreras4, Susan G. Hilsenbeck4, Wendy A. Woodward3, Sunil Krishnan3, Jenny C. Chang1,4,*? and Jeffrey M. Rosen1,2,??
1Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
2Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
3Radiation Oncology, M. D. Anderson Cancer Center, Houston, TX 77030, USA.
4Breast Center, Baylor College of Medicine, Houston, TX 77030, USA.
Breast cancer metastasis and disease recurrence are hypothesized to result from residual cancer stem cells, also referred to as tumor-initiating cells, which evade initial treatment. Using both syngeneic mouse and human xenograft models of triple-negative breast cancer, we have demonstrated that a subpopulation enriched in cancer stem cells was more resistant to treatment with 6 gray of ionizing radiation than the bulk of the tumor cells, and accordingly their relative proportion increased 48 to 72 hours after ionizing radiation treatment. In contrast, we achieved a larger reduction in tumor size without a concomitant increase in the percentage of cancer stem cells by treating with local hyperthermia for 20 minutes at 42°C after ionizing radiation using intravenously administered, optically activated gold nanoshells. Forty-eight hours after treatment, cells derived from the tumors treated with ionizing radiation plus hyperthermia exhibited both a marked decrease in tumorigenicity and a more differentiated phenotype than mock- and ionizing radiation–treated tumors. Thus, we have confirmed that these cancer stem cells are responsible for accelerated repopulation in vivo and demonstrated that hyperthermia sensitizes this cell population to radiation treatment. These findings suggest that local hyperthermia delivered by gold nanoshells plus radiation can eliminate radioresistant breast cancer stem cells.
