Photothermal effects of supramolecularly assembled gold nanoparticles for the targeted treatment of cancer cells.
Photothermal effects of supramolecularly assembled gold nanoparticles for the targeted treatment of cancer cells.
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DOI：
10.1002/anie.201000062
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发表时间：
2010-05-17
影响因子：
16.6
通讯作者：
Tseng, Hsian-Rong
中科院分区：
文献类型：
--
作者：
Wang, Shutao;Chen, Kuan-Ju;Wu, Ting-Hsiang;Wang, Hao;Lin, Wei-Yu;Ohashi, Minori;Chiou, Pei-Yu;Tseng, Hsian-Rong
贵金属纳米结构具有独特的光物理性质，被认为是光热治疗癌症的主要候选药物。[1-4]通常，这些纳米结构的光热性质可以通过操纵它们的尺寸和形状来控制。[4，5]在过去的十年中，已经致力于生产各种金纳米结构，例如纳米颗粒，[6，7]纳米壳，[8-10]纳米棒，[11，12]和纳米笼，[5，13，14]它们能够克服有机染料基光热剂的限制，[7]例如低光吸收和不希望的光漂白。为了获得/产生足够的能量来破坏肿瘤细胞，这些基于纳米结构的试剂的尺寸需要在数十至数百nm的范围内。[15]然而，相对“大”尺寸的试剂通常导致较差的生物清除（即，在肝、脾和肾中的积累），这是其体内应用的主要障碍。[16-18]或者，贵金属纳米结构的光物理性质可以通过自组装形成聚集体而系统地改变。[19-30]抗体辅助的Au纳米颗粒在细胞膜上或细胞内环境中的聚集导致光热性能的增强[31]，这是与组装结构相关的集体效应[32，33]的结果。因此，小的贵金属构建块，即直径小于8 nm的贵金属胶体的自组装[16-18]（与肾清除率相容）将是一种有前途的新一类贵金属光热剂的方法。最近，我们展示了一种方便，灵活，和模块化自组装方法，通过基于β-环糊精的多价分子识别来制备尺寸可控的超分子纳米颗粒（SNPs）（CD）和金刚烷（Ad）基序。[34]通过混合三种分子结构单元制备尺寸受控的SNP：1）直径约为1.9 nm的Ad接枝的聚酰胺胺树状聚合物，2）CD接枝的支链聚乙烯亚胺（CD-PEI），和3）Ad接枝的聚乙二醇（Ad-PEG）。我们假设这种超分子合成方法可以进一步探索，以组装无机构建块（即，2 nm Au胶体）到一个集合的Au超分子纳米粒子（Au-SNP）具有定义的大小。我们预计，所得到的Au-SNP可能表现出增强的光热效应[19]，因此可能是光热癌症治疗的有希望的候选药物。超分子方法的使用使得[34，35]能够方便地掺入靶向配体以提供靶特异性Au-SNP。
Noble-metal nanostructures with unique photophysical properties have been considered as prime candidate agents for the photothermal treatment of cancer.[1–4] Typically, the photothermal properties of these nanostructures can be controlled by manipulating their sizes and shapes.[4, 5] Over the past decade, significant endeavors have been devoted to the production of a variety of gold nanostructures, such as nanoparticles,[6, 7] nanoshells,[8–10] nanorods,[11, 12] and nanocages,[5, 13, 14] which are able to overcome limitations of organicdye-based photothermal agents,[7] such as low light absorption and undesired photobleaching. For sufficient energy to be harvested/generated to damage tumor cells, the size of these nanostructure-based agents are required in the range of tens to hundreds nm.[15] However, the relatively “large” size of the agents often leads to poor bioclearance (ie, accumulation in the liver, spleen, and kidneys), which is a major obstacle to their in vivo application.[16–18] Alternatively, the photophysical properties of noble-metal nanostructures can be altered systematically by the formation of aggregates through self-assembly.[19–30] The antibodyassisted aggregation of Au nanoparticles on cell membranes or in intracellular environments led to the enhancement of photothermal performance [31] as a result of the collective effects [32, 33] associated with the assembled structures. Therefore, the self-assembly of small noblemetal building blocks, that is, noble-metal colloids with diameters of less than 8 nm [16–18](compatible with renal clearance) would be a promising approach toward a new class of noblemetal photothermal agents.Recently, we demonstrated a convenient, flexible, and modular self-assembly approach for the preparation of supramolecular nanoparticles (SNPs) of controlled size through multivalent molecular recognition based on β-cyclodextrin (CD) and adamantane (Ad) motifs.[34] Sizecontrolled SNPs were prepared by mixing three molecular building blocks: 1) an Ad-grafted polyamidoamine dendrimer with a diameter of approximately 1.9 nm, 2) CD-grafted branched polyethylenimine (CD-PEI), and 3) Ad-grafted polyethylene glycol (Ad-PEG). We hypothesized that such a supramolecular synthetic approach could be further explored to assemble inorganic building blocks (ie, 2 nm Au colloids) into a collection of Au supramolecular nanoparticles (Au-SNPs) with defined sizes. We anticipated that the resulting Au-SNPs might exhibit enhanced photothermal effects [19] and could thus be promising candidate agents for photothermal cancer treatment. The use of a supramolecular approach enables [34, 35] the convenient incorporation of targeting ligands to provide target-specific Au-SNPs.