Near-Infrared Plasmonic Assemblies of Gold Nanoparticles with Multimodal Function for Targeted Cancer Theragnosis.

Near-Infrared Plasmonic Assemblies of Gold Nanoparticles with Multimodal Function for Targeted Cancer Theragnosis.
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DOI:
10.1038/s41598-017-17714-2
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发表时间:
2017-12-11
期刊:
影响因子:
4.6
通讯作者:
Lee J
Lee J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kim SE;Lee BR;Lee H;Jo SD;Kim H;Won YY;Lee J

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在这里,我们报告了一种新的组装结构的近红外等离子体金纳米粒子(AuNPs),同时具有光声(PA)和光热(PT)性能。等离子体AuNP组装的模板是短双链DNA(sh-dsDNA)和人甲基结合域蛋白1(MBD 1)之间的生物缀合物。MBD 1结合sh-dsDNA序列内的甲基化胞嘧啶-鸟嘌呤二核苷酸(mCG)。工程改造的MBD 1上的六组氨酸肽作为AuNP合成的成核位点发挥作用,允许构建杂交缀合物sh-dsDNA-MBD 1-AuNP(称为DMA)。通过改变sh-dsDNA骨架的长度和两个相邻mCG之间的间隔基,我们合成了三种不同的DMA(DMA_5mCG、DMA_9mCG和DMA_21mCG),其中DMA_21mCG与等离子体金纳米棒相比表现出相当的光热信号和令人惊讶的更高的光声信号。此外,表皮生长因子受体I(EGFR)结合肽在遗传上附着于DMA_21mCG的MBD 1,使其能够有效地内吞到EGFR过表达的癌细胞中。值得注意的是,MBD 1的变性分解了DMA,并因此释放了单独的小AuNP(<5 nm),其可以通过肾排泄容易地从体内清除,而不会引起积累/毒性问题。这种基于DMA的新方法为基于同时PA成像和PT治疗的靶向癌症治疗提供了一个有前途的平台。
Here we report a novel assembly structure of near-infrared plasmonic gold nanoparticles (AuNPs), possessing both photoacoustic (PA) and photothermal (PT) properties. The template for the plasmonic AuNP assembly is a bioconjugate between short double-strand DNA (sh-dsDNA) and human methyl binding domain protein 1 (MBD1). MBD1 binds to methylated cytosine-guanine dinucleotides (mCGs) within the sequence of sh-dsDNA. Hexahistidine peptides on the engineered MBD1 function as a nucleation site for AuNP synthesis, allowing the construction of hybrid conjugates, sh-dsDNA-MBD1-AuNPs (named DMAs). By varying the length of sh-dsDNA backbone and the spacer between two adjacent mCGs, we synthesized three different DMAs (DMA_5mCG, DMA_9mCG, and DMA_21mCG), among which DMA_21mCG exhibited a comparable photothermal and surprisingly a higher photoacoustic signals, compared to a plasmonic gold nanorod. Further, epidermal growth factor receptor I (EGFR)-binding peptides are genetically attached to the MBD1 of DMA_21mCG, enabling its efficient endocytosis into EGFR-overexpressing cancer cells. Notably, the denaturation of MBD1 disassembled the DMA and accordingly released the individual small AuNPs (<5 nm) that can be easily cleared from the body through renal excretion without causing accumulation/toxicity problems. This DMA-based novel approach offers a promising platform for targeted cancer theragnosis based on simultaneous PA imaging and PT therapy.
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