在小鼠中的一项新的研究报告说，将金纳米粒子注射到乳腺肿瘤之中可使该肿瘤细胞对放疗更为敏感。 金纳米壳技术目前正在进行临床试验，它可能会给罹患难治性乳腺癌患者提供所需的杀灭肿瘤细胞的额外的推动力。
人们抗击乳腺癌所遭遇的最大的障碍之一是该肿瘤中存在着一小群的肿瘤干细胞，它们比主体的肿瘤细胞对放疗和化疗有着更大的抵抗力；治疗后肿瘤的再生常常归咎于这些肿瘤干细胞。 为寻求杀灭尽可能多的癌症细胞，科学家们发明了伴随放疗和其它常规疗法的新技术，其中包括热疗，即让身体组织接触高达45摄氏度（113华氏度）的高温。 以往的研究显示，灼热的温度可损伤并杀死癌症细胞，并可使癌症干细胞对放疗更为敏感，同时对正常组织的损伤也是最小的。 然而，在过去的几年中，对乳腺癌实行热疗已大体上被人抛弃，因为给肿瘤快速加温但又不灼伤周边组织是困难的。 为了解决这一问题，Rachel Atkinson及其同事设计制造了金纳米粒子来给肿瘤干细胞加温，并使它们对放疗变得更为敏感。 他们证明，施行使用金纳米粒子的热疗可有效地压制小鼠乳腺癌模型中的癌症干细胞。
黄金是纳米球壳（即极小的球状硅石块）的理想性的涂层，因为它在生物组织中要比其它金属的毒性小。在该试验中，人们向小鼠的肿瘤中直接注射了一剂金纳米球壳。这些金纳米球壳会渗漏到血管之外及在肿瘤内聚集，并在被激光激活的时候造成局部加温。这一由纳米球壳所诱导的加温阻止了肿瘤细胞对由放疗所导致的双股DNA断裂的修复，因而增加了它们对放疗的敏感性。在注射了金纳米球壳一天之后，小鼠接受了单一剂量的放疗或单一剂量的放疗及20分钟的热疗。在治疗2天之后，那些仅仅接受放疗的小鼠的癌症细胞分裂速度更快并会比那些没有接受治疗的小鼠更为活跃地形成更多的肿瘤。另一方面，那些接受放疗加热疗的小鼠，其癌症细胞的萌生速度较慢，形成的肿瘤较少，表明热疗阻止了癌症干细胞的生长并可能改变了其迅速生长的特性。研究人员接着又做了更进一步的试验：对在小鼠体内繁殖的人的乳腺肿瘤细胞重复了以上的试验。他们再一次看到，由纳米球壳诱导的加温效应使得人的乳腺肿瘤干细胞对放疗变得更为敏感。（生物谷Bioon.com）
生物谷推荐英文摘要：
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.
