Exploiting active nuclear import for efficient delivery of Auger electron emitters into the cell nucleus

Rosenkranz, A.A.; Slastnikova, T.A.; Durymanov, M.O.; Georgiev, G.P.; Sobolev, A.S.

Авторы: Rosenkranz Andrey A., Slastnikova Tatiana A., Durymanov Mikhail O., Georgiev Georgii P., Sobolev Alexander S.
Журнал: International Journal of Radiation Biology
Том: 99
Номер: 1
Год издания: 2023
Издательство: Taylor & Francis
Местоположение издательства: United Kingdom
Первая страница: 28
Последняя страница: 38
DOI: 10.1080/09553002.2020.1815889
Аннотация: Background: The most attractive features of Auger electrons (AEs) in cancer therapy are their extremely short range and sufficiently high linear energy transfer (LET) for a majority of them. The cytotoxic effects of AE emitters can be realized only in close vicinity to sensitive cellular targets and they are negligible if the emitters are located outside the cell. The nucleus is considered the compartment most sensitive to high LET particles. Therefore, the use of AE emitters could be most useful in specific recognition of a cancer cell and delivery of AE emitters into its nucleus. Purpose: This review describes the studies aimed at developing effective anticancer agents for the delivery of AE emitters to the nuclei of target cancer cells. The use of peptide-based conju- gates, nanoparticles, recombinant proteins, and other constructs for AE emitter targeted intranu- clear delivery as well as their advantages and limitations are discussed.Conclusion: Transport from the cytoplasm to the nucleus along with binding to the cancer cell is one of the key stages in the delivery of AE emitters; therefore, several constructs for exploitation of this transport have been developed. The transport is carried out through a nuclear pore com- plex (NPC) with the use of specific amino acid nuclear localization sequences (NLS) and carrier pro- teins named importins, which are located in the cytosol. Therefore, the effectiveness of NLS- containing delivery constructs designed to provide energy-dependent transport of AE emitter into the nuclei of cancer cells also depends on their efficient entry into the cytosol of the target cell.
Добавил в систему: Соболев Александр Сергеевич

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