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使用适配体偶联纳米棒对混合癌细胞进行选择性光热治疗。

Selective photothermal therapy for mixed cancer cells using aptamer-conjugated nanorods.

作者信息

Huang Yu-Fen, Sefah Kwame, Bamrungsap Suwussa, Chang Huan-Tsung, Tan Weihong

机构信息

Center for Research at the Bio/Nano Interface, Department of Chemistry, Shands Cancer Center, Genetics Institute, and McKnight Brain Institute, University of Florida, Gainesville, Florida 32611-7200, USA.

出版信息

Langmuir. 2008 Oct 21;24(20):11860-5. doi: 10.1021/la801969c. Epub 2008 Sep 26.

Abstract

Safe and effective photothermal therapy depends on efficient delivery of heat for killing cells and molecular specificity for targeting cells. To address these requirements, we have designed an aptamer-based nanostructure which combines the high absorption efficiency of Au-Ag nanorods with the target specificity of molecular aptamers, a combination resulting in the development of an efficient and selective therapeutic agent for targeted cancer cell photothermal destruction. Most nanomaterials, such as gold nanoshells or nanorods (NRs), require a relatively high power of laser irradiation (1 x 10 (5)-1 x 10 (10) W/m (2)). In contrast, the high absorption characteristic of our Au-Ag NRs requires only 8.5 x 10 (4) W/m (2) laser exposure to induce 93 (+/-11)% cell death of NR-aptamer-labeled cells. Aptamers, the second component of the nanostructure, are generated from a cell-SELEX (systematic evolution of ligands by exponential enrichment) process and can be easily selected for specific recognition of individual tumor cell types without prior knowledge of the biomarkers for the cell. When tested with both cell suspensions and artificial solid tumor samples, these aptamer conjugates were shown to have excellent hyperthermia efficiency and selectivity. Under a specific laser intensity and duration of laser exposure, about 50 (+/-1)% of target (CEM) cells were severely damaged, while more than 87 (+/-1)% of control (NB-4) cells remained intact in a suspension cell mixture. These results indicate that the Au-Ag nanorod combination offers selective and efficient photothermal killing of targeted tumor cells, thus satisfying the two key challenges noted above. Consequently, for future in vivo application, it is fully anticipated that the tumor tissue will be selectively destroyed at laser energies which will not harm the surrounding normal tissue.

摘要

安全有效的光热疗法取决于热的有效传递以杀死细胞以及靶向细胞的分子特异性。为满足这些要求,我们设计了一种基于适配体的纳米结构,它将金 - 银纳米棒的高吸收效率与分子适配体的靶向特异性相结合,这种结合促成了一种用于靶向癌细胞光热破坏的高效且选择性的治疗剂的开发。大多数纳米材料,如金纳米壳或纳米棒(NRs),需要相对较高功率的激光照射(1×10⁵ - 1×10¹⁰ W/m²)。相比之下,我们的金 - 银纳米棒的高吸收特性仅需8.5×10⁴ W/m²的激光照射就能诱导NR - 适配体标记细胞发生93(±11)%的细胞死亡。适配体是纳米结构的第二个组成部分,通过细胞SELEX(指数富集配体系统进化)过程产生,无需事先了解细胞的生物标志物,就能轻松选择用于特异性识别单个肿瘤细胞类型。当在细胞悬液和人工实体瘤样本中进行测试时,这些适配体缀合物显示出优异的热疗效率和选择性。在特定的激光强度和激光照射持续时间下,在悬浮细胞混合物中,约50(±1)%的靶标(CEM)细胞受到严重损伤,而超过87(±1)%的对照(NB - 4)细胞保持完整。这些结果表明,金 - 银纳米棒组合能对靶向肿瘤细胞进行选择性且高效的光热杀伤,从而满足了上述两个关键挑战。因此,对于未来的体内应用,可以完全预期在不会损害周围正常组织的激光能量下肿瘤组织将被选择性破坏。

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