Sobolev Alexander S
Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia.
Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia.
Front Pharmacol. 2018 Aug 27;9:952. doi: 10.3389/fphar.2018.00952. eCollection 2018.
This review describes artificial modular nanotransporters (MNTs) delivering their cargos into target cells and then into the nuclei - the most vulnerable cell compartment for most anticancer agents and especially for radionuclides emitting short-range particles. The MNT strategy uses natural subcellular transport processes inherent in practically all cells including cancer cells. The MNTs use these processes just as a passenger who purchased tickets for a multiple-transfer trip making use of different kinds of public transport to reach the desired destination. The MNTs are fusion polypeptides consisting of several parts, replaceable modules, accomplishing binding to a specific receptor on the cell and subsequent internalization, endosomal escape and transport into the cell nucleus. Radionuclides emitting short-range particles, like Auger electron emitters, acquire cell specificity and significantly higher cytotoxicity both and when delivered by the MNTs into the nuclei of cancer cells. MNT modules are interchangeable, allowing replacement of receptor recognition modules, which permits their use for different types of cancer cells and, as a cocktail of several MNTs, for targeting several tumor-specific molecules for personalized medicine.
本综述描述了人工模块化纳米转运体（MNTs），它们将货物递送至靶细胞，然后进入细胞核——这是大多数抗癌药物尤其是发射短程粒子的放射性核素最易作用的细胞区室。MNT策略利用了包括癌细胞在内的几乎所有细胞固有的天然亚细胞转运过程。MNTs利用这些过程，就像一名购买了多次换乘车票的乘客，利用不同种类的公共交通工具到达理想目的地一样。MNTs是由几个部分组成的融合多肽，即可替换模块，可实现与细胞上特定受体的结合以及随后的内化、内体逃逸并转运至细胞核。发射短程粒子的放射性核素，如俄歇电子发射体，当由MNTs递送至癌细胞核时，会获得细胞特异性并显著提高细胞毒性。MNT模块是可互换的，允许替换受体识别模块，这使得它们可用于不同类型的癌细胞，并且作为几种MNTs的混合物，可用于靶向多种肿瘤特异性分子以实现个性化医疗。
