ИСТИНА

Purpose/Introduction. Most of emitted Auger electrons have ranges of several tens or hundreds of nanometers. This fact implies a necessity of not only a targeted delivery of Auger electron emitters to a specific cell but also delivery into the cell nucleus as one of the most vulnerable cell site. The main purpose of our approach is to create such a vehicle that could combine (i) recognition of a target cell, (ii) subsequent endocytosis, (iii) escape from endocytic compartments and, finally, (iv) transport into the cell nucleus. Our strategy is to exploit natural subcellular transport processes inherent in practically all cells including cancer cells. Methods. We have created modular nanotransporters (MNT), chimeric polypeptides, consisting of several parts, replaceable modules, accomplishing all the above-mentioned (i-iv) functions (1). Results. Radionuclides emitting short-range particles, like Auger electron emitters, acquire cell specificity and significantly higher cytotoxicity both in vitro and in vivo when delivered by the MNT 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(2; 3). Discussion/Conclusion. Auger electron emitters carried by MNT were shown to demonstrate high cytotoxicity for cancer cells and exhibit promising therapeutic potential in murine cancer models. A strong point of MNT is the substitutability of their modules, offering a stimulating potential of generating an MNT cocktail with an optimal combination of ligand modules and subcellular localizing sequences tailored to the molecular profile of an individual patient’s tumor. This work was supported by the Russian Science Foundation, grant no. 17-14-01304. 1. Sobolev A. 2018. Front. Pharmacol. 9:952 2. Slastnikova T, et al. 2017. International journal of nanomedicine 12:395-410 3. Rosenkranz A, et al. 2018. Front. Pharmacol. 9:1331