Treating cancer stem cells and cancer metastasis using glucose-coated gold nanoparticles.
Treating cancer stem cells and cancer metastasis using glucose-coated gold nanoparticles.
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DOI：
10.2147/ijn.s72144
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发表时间：
2015
影响因子：
8
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Hu C;Niestroj M;Yuan D;Chang S;Chen J
癌症是人类死亡的主要原因之一。当癌症从原发肿瘤部位扩散到各个器官（例如骨、肺、肝，然后是脑）时，癌症就会变得难以治愈。与实体瘤细胞不同，癌症干细胞和转移性癌细胞在从来源转移到体内其他部位时以非附着（悬浮）形式生长。由于非附着生长的性质，转移通常首先在循环系统中检测到，例如在原发肿瘤附近的淋巴结中。过去几十年的癌症研究主要集中在实体瘤的治疗上，但治疗癌症干细胞和癌症转移的靶向疗法尚未开发出来。由于癌症比正常细胞代谢更快，消耗更多的葡萄糖，因此本研究选择葡萄糖作为靶向癌细胞的试剂。特别是，通过将金纳米颗粒（GNP）与硫代聚乙二醇（聚乙二醇）和硫代葡萄糖共价结合，产生的功能化GNP（Glu-GNP）可用于癌症转移和癌症干细胞的靶向治疗。选择悬浮癌细胞THP-1（源自急性单核细胞白血病患者的人单核细胞系）是因为它具有与癌症干细胞相似的特性，并已被用作体外研究的转移性癌细胞模型。为了利用癌细胞比正常细胞更高的葡萄糖消耗，筛选不同的饥饿期以达到最佳的治疗效果。然后使用 Glu-GNP 喂养癌细胞，然后进行 X 射线照射处理。为了进行比较，还研究了实体瘤 MCF-7 细胞（乳腺癌细胞系）。我们的辐照实验结果表明，Glu-GNPs 是比 MCF-7 细胞更好的治疗 THP-1 细胞的辐照增敏剂，或者说 Glu-GNPs 比单独 X 射线辐照和单独 GNP 治疗增强 THP-1 细胞的癌症杀伤力 20% 以上。这一发现可以帮助肿瘤学家设计针对癌症干细胞和癌症转移的治疗策略。
Cancer ranks among the leading causes of human mortality. Cancer becomes intractable when it spreads from the primary tumor site to various organs (such as bone, lung, liver, and then brain). Unlike solid tumor cells, cancer stem cells and metastatic cancer cells grow in a non-attached (suspension) form when moving from their source to other locations in the body. Due to the non-attached growth nature, metastasis is often first detected in the circulatory systems, for instance in a lymph node near the primary tumor. Cancer research over the past several decades has primarily focused on treating solid tumors, but targeted therapy to treat cancer stem cells and cancer metastasis has yet to be developed. Because cancers undergo faster metabolism and consume more glucose than normal cells, glucose was chosen in this study as a reagent to target cancer cells. In particular, by covalently binding gold nanoparticles (GNPs) with thio-PEG (polyethylene glycol) and thio-glucose, the resulting functionalized GNPs (Glu-GNPs) were created for targeted treatment of cancer metastasis and cancer stem cells. Suspension cancer cell THP-1 (human monocytic cell line derived from acute monocytic leukemia patients) was selected because it has properties similar to cancer stem cells and has been used as a metastatic cancer cell model for in vitro studies. To take advantage of cancer cells’ elevated glucose consumption over normal cells, different starvation periods were screened in order to achieve optimal treatment effects. Cancer cells were then fed using Glu-GNPs followed by X-ray irradiation treatment. For comparison, solid tumor MCF-7 cells (breast cancer cell line) were studied as well. Our irradiation experimental results show that Glu-GNPs are better irradiation sensitizers to treat THP-1 cells than MCF-7 cells, or Glu-GNPs enhance the cancer killing of THP-1 cells 20% more than X-ray irradiation alone and GNP treatment alone. This finding can help oncologists to design therapeutic strategies to target cancer stem cells and cancer metastasis.