Abstract

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 conjugates, nanoparticles, recombinant proteins, and other constructs for AE emitter targeted intranuclear 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 complex (NPC) with the use of specific amino acid nuclear localization sequences (NLS) and carrier proteins 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.

中文翻译：

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利用活跃的核输入将俄歇电子发射器有效地输送到细胞核中

摘要

背景

俄歇电子 (AE) 在癌症治疗中最吸引人的特征是它们中的大多数具有极短的射程和足够高的线性能量转移 (LET)。AE 发射器的细胞毒性作用只能在敏感的细胞靶标附近实现，如果发射器位于细胞外，则可以忽略不计。细胞核被认为是对高 LET 粒子最敏感的隔室。因此，AE 发射器的使用在癌细胞的特异性识别和将 AE 发射器递送到其细胞核中可能是最有用的。

目的

这篇综述描述了旨在开发有效抗癌剂以将 AE 发射体递送至靶癌细胞核的研究。讨论了基于肽的偶联物、纳米粒子、重组蛋白和其他结构在 AE 发射体靶向核内递送中的应用及其优点和局限性。

结论

从细胞质到细胞核的运输以及与癌细胞的结合是 AE 发射体传递的关键阶段之一；因此，开发了几种利用这种传输的结构。运输是通过核孔复合体 (NPC) 进行的，使用特定的氨基酸核定位序列 (NLS) 和名为 importins 的载体蛋白，它们位于胞质溶胶中。因此，旨在提供能量依赖性 AE 发射体向癌细胞核内转运的含 NLS 递送结构的有效性也取决于它们是否有效进入靶细胞的胞质溶胶。