Polypod-like structured guanine-rich oligonucleotide aptamer as a selective and cytotoxic nanostructured DNA to cancer cells

Polypod-like structured guanine-rich oligonucleotide aptamer as a selective and cytotoxic nanostructured DNA to cancer cells
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多足类结构的富含鸟嘌呤的寡核苷酸适体作为对癌细胞的选择性和细胞毒性纳米结构DNA

DOI:
10.1080/1061186x.2020.1830407
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发表时间:
2020
影响因子:
4.5
通讯作者:
Sakuma Shinji
Sakuma Shinji
中科院分区:
医学3区
文献类型:
--
作者:
Mohri Kohta;Hayashi Emi;Nishino Manato;Matsushita Nao;Tanishita Sohei;Nishikawa Makiya;Sakuma Shinji

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富含鸟嘌呤的寡核苷酸(GRO)具有高度的选择性、亲和性和抗肿瘤细胞增殖活性,有望成为一种有效的抗肿瘤药物。在这项研究中,为了增加GRO 29 A(一种29聚体GRO适体)针对核仁素(癌细胞中过表达的蛋白质)的效力,将GRO 29 A分别掺入三个或六个多足样结构DNA(多足DNA)、三足DNA或六足DNA的荚中。设计了由一个三足DNA和三个GRO 29 A组成的多足状结构的GRO,tri-G3,或hexa-G1,hexa-G3或hexa-G6,其中每个分别包含一个六足DNA和一个,三个或六个GRO 29 A。除hexa-G6外,以高产率制备Tri-G3、hexa-G1和hexa-G3。在生理盐条件下,多足状结构的GRO具有四链体结构,并且在含有血清的缓冲液中以较慢的速率降解。使用荧光标记的DNA样品的细胞相互作用实验表明,核仁素阳性MCF-7细胞对hexa-G3的摄取比GRO 29 A高2倍以上,并且相互作用越来越依赖于结构中GRO 29 A的数量。Hexa-G3对MCF-7细胞的增殖抑制率超过40%,但对CHO细胞无抑制作用。这些结果表明,多足状结构的GRO是有用的DNA适体,对核仁素阳性癌细胞具有高选择性和细胞毒性。
Guanine-rich oligonucleotide (GRO) can be developed as an effective anticancer agent owing to its high selectivity, affinity and antiproliferative activity in cancer cells. In this study, to increase the potency of GRO29A, a 29-mer GRO aptamer against nucleolin, an overexpressed protein in cancer cells, GRO29A was incorporated into three or six pods of polypod-like structured DNA (polypodna), tripodna or hexapodna, respectively. The polypod-like structured GROs, tri-G3, consisting of one tripodna and three GRO29A, or hexa-G1, hexa-G3 or hexa-G6, each of which comprises one hexapodna and one, three or six GRO29A, respectively, were designed. Tri-G3, hexa-G1 and hexa-G3 were prepared in high yield, except for hexa-G6. Polypod-like structured GROs had quadruplex structures under physiological salt conditions, and degraded at a slower rate in buffer containing serum. Cellular interaction experiments using fluorescently labelled DNA samples showed that the uptake of hexa-G3 by nucleolin-positive MCF-7 cells was more than 2-fold higher than GRO29A, and the interaction was increasingly dependent on the number of GRO29A in the structures. Hexa-G3 inhibited the proliferation of MCF-7 cells in more than 40%, but not of CHO cells. These results indicate that polypod-like structured GROs are useful DNA aptamers with high selectivity and cytotoxicity against nucleolin-positive cancer cells.
DNA 树枝状聚合物的免疫刺激活性
DOI: --
发表时间: 2021
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