Toward the Selection of Cell Targeting Aptamers with Extended Biological Functionalities to Facilitate Endosomal Escape of Cargoes.
Toward the Selection of Cell Targeting Aptamers with Extended Biological Functionalities to Facilitate Endosomal Escape of Cargoes.
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DOI：
10.3390/biomedicines5030051
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发表时间：
2017-08-24
期刊：
影响因子：
4.7
通讯作者：
Burke DH
中科院分区：
文献类型：
--
作者：
Tawiah KD;Porciani D;Burke DH
在过去的几十年里，高度特异的分子已经取得了令人兴奋和快速的发展，以结合在恶性肿瘤细胞表面过度表达的癌症抗原。纳米医学的目标是利用这些配体来产生纳米级的平台，用于靶向癌症治疗，并且这样做的时候，靶外效应可以忽略不计。适配子是一种结构化的核酸，可以与从小分子和蛋白质到整个细胞或病毒的特定分子靶标结合。它们是通过称为SELEX(指数富集法的配体的系统进化)的扩增和浓缩的迭代过程来选择的，在该过程中，将一个组合寡核苷酸文库暴露在目标靶上几轮重复。能够结合和内化到恶性肿瘤细胞中的核酸配体在体外和体内都被广泛用作靶向递送治疗有效载荷的工具。然而，目前的细胞靶向适体平台受到限制，减缓了它们进入临床的速度。对于货物必须到达胞质才能发挥其生物活性的应用尤其如此，因为通常只有一小部分内吞的货物能够转移到胞质中。需要创新的技术和选择策略来加强细胞质的传递。在这篇综述中，我们描述了目前用于产生靶向癌细胞的适配子的选择方法，并强调了一些影响货物有效内体逃逸的因素。我们还概述了用于改善和监测治疗货物的内体逃逸的最有希望的策略。我们重点介绍的方法是利用可能被纳入SELEX过程的工具和技术。创新的选择方案可以识别具有扩展的生物学功能的适配子，从而允许治疗药物的有效胞浆转位。这反过来可能会促进这些平台成功地转化为临床应用。
Over the past decades there have been exciting and rapid developments of highly specific molecules to bind cancer antigens that are overexpressed on the surfaces of malignant cells. Nanomedicine aims to exploit these ligands to generate nanoscale platforms for targeted cancer therapy, and to do so with negligible off-target effects. Aptamers are structured nucleic acids that bind to defined molecular targets ranging from small molecules and proteins to whole cells or viruses. They are selected through an iterative process of amplification and enrichment called SELEX (systematic evolution of ligands by exponential enrichment), in which a combinatorial oligonucleotide library is exposed to the target of interest for several repetitive rounds. Nucleic acid ligands able to bind and internalize into malignant cells have been extensively used as tools for targeted delivery of therapeutic payloads both in vitro and in vivo. However, current cell targeting aptamer platforms suffer from limitations that have slowed their translation to the clinic. This is especially true for applications in which the cargo must reach the cytosol to exert its biological activity, as only a small percentage of the endocytosed cargo is typically able to translocate into the cytosol. Innovative technologies and selection strategies are required to enhance cytoplasmic delivery. In this review, we describe current selection methods used to generate aptamers that target cancer cells, and we highlight some of the factors that affect productive endosomal escape of cargoes. We also give an overview of the most promising strategies utilized to improve and monitor endosomal escape of therapeutic cargoes. The methods we highlight exploit tools and technologies that can potentially be incorporated in the SELEX process. Innovative selection protocols may identify aptamers with extended biological functionalities that allow effective cytosolic translocation of therapeutics. This in turn may facilitate successful translation of these platforms into clinical applications.
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影响因子：
46.9
作者：
Dassie, Justin P.;Liu, Xiu-ying;Thomas, Gregory S.;Whitaker, Ryan M.;Thiel, Kristina W.;Stockdale, Katie R.;Meyerholz, David K.;McCaffrey, Anton P.;McNamara, James O., II;Giangrande, Paloma H.
通讯作者：
Giangrande, Paloma H.
DOI：
10.1038/mtna.2016.73
发表时间：
2016-09-20
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
通讯作者：
--
DOI：
10.3390/ph5111177
发表时间：
2012-11-01
期刊：
Pharmaceuticals (Basel, Switzerland)
影响因子：
--
作者：
Erazo-Oliveras A;Muthukrishnan N;Baker R;Wang TY;Pellois JP
通讯作者：
Pellois JP
影响因子：
4.7
作者：
Kruspe S;Giangrande PH
通讯作者：
Giangrande PH
选择针对未糖基化的EGFRVIII胞外域的适体，细胞内递送降低膜结合的EGFRVIII并诱导细胞凋亡。
影响因子：
3.7
作者：
Liu Y;Kuan CT;Mi J;Zhang X;Clary BM;Bigner DD;Sullenger BA
通讯作者：
Sullenger BA