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低能电子在癌症治疗中的应用

The Exploitation of Low-Energy Electrons in Cancer Treatment.

作者信息

Rezaee Mohammad, Hill Richard P, Jaffray David A

机构信息

Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Ontario Cancer Institute and Campbell Family Institute for Cancer Research and Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada.

出版信息

Radiat Res. 2017 Aug;188(2):123-143. doi: 10.1667/RR14727.1. Epub 2017 May 30.

Abstract

Given the distinct characteristics of low-energy electrons (LEEs), particularly at energies less than 30 eV, they can be applied to a wide range of therapeutic modalities to improve cancer treatment. LEEs have been shown to efficiently produce complex molecular damage resulting in substantial cellular toxicities. Since LEEs are produced in copious amounts from high-energy radiation beam, including photons, protons and ions; the control of LEE distribution can potentially enhance the therapeutic radio of such beams. LEEs can play a substantial role in the synergistic effect between radiation and chemotherapy, particularly halogenated and platinum-based anticancer drugs. Radiosensitizing entities containing atoms of high atomic number such as gold nanoparticles can be a source of LEE production if high-energy radiation interacts with them. This can provide a high local density of LEEs in a cell and produce cellular toxicity. Auger-electron-emitting radionuclides also create a high number of LEEs in each decay, which can induce lethal damage in a cell. Exploitation of LEEs in cancer treatment, however, faces a few challenges, such as dosimetry of LEEs and selective delivery of radiosensitizing and chemotherapeutic molecules close to cellular targets. This review first discusses the rationale for utilizing LEEs in cancer treatment by explaining their mechanism of action, describes theoretical and experimental studies at the molecular and cellular levels, then discusses strategies for achieving modification of the distribution and effectiveness of LEEs in cancerous tissue and their associated clinical benefit.

摘要

鉴于低能电子(LEEs)的独特特性,特别是在能量低于30电子伏特时,它们可应用于广泛的治疗方式以改善癌症治疗。已证明低能电子能有效产生复杂的分子损伤,从而导致显著的细胞毒性。由于低能电子大量产生于高能辐射束,包括光子、质子和离子;控制低能电子的分布可能会提高此类辐射束的治疗效果。低能电子在放疗与化疗的协同作用中可发挥重要作用,尤其是与卤代和铂类抗癌药物。如果高能辐射与含高原子序数原子的放射增敏实体(如金纳米颗粒)相互作用,它们可成为低能电子的产生源。这可在细胞中提供高局部密度的低能电子并产生细胞毒性。俄歇电子发射放射性核素在每次衰变时也会产生大量低能电子,可在细胞中诱导致命损伤。然而,在癌症治疗中利用低能电子面临一些挑战,如低能电子的剂量测定以及将放射增敏和化疗分子选择性递送至细胞靶点附近。本综述首先通过解释其作用机制来讨论在癌症治疗中利用低能电子的基本原理,描述分子和细胞水平的理论与实验研究,然后讨论实现改变低能电子在癌组织中的分布和有效性及其相关临床益处的策略。

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