放射治疗可降低瘤中原药激活的氧化物
Zexuan Ding1,2, Zhibin Guo1, Yuedan Zheng1
1Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Journal of the American Chemical Society
|May 20, 2022
概括
放射治疗 (X射线) 精确地通过水放射解激活新型N氧化物前药物. 这种策略显示出显著的抗癌效应,提供了有针对性的癌症治疗方法,降低了全身毒性.
科学领域:
- 放射化学
- 癌症学
- 药物输送系统
背景情况:
- 有针对性的癌症治疗旨在通过激活瘤内的药物来最大限度地降低全身毒性.
- 在瘤学中,开发可空间时间控制的前药激活方法仍然是一个重大挑战.
- 放射治疗提供精确的深层组织透,使其成为现场前药物激活的潜在触发器.
研究的目的:
- 开发和验证使用X射线放射治疗的新型前药激活策略.
- 通过辐射诱导的化电子来研究N-氧化物的减少机制.
- 通过放射治疗激活的N-氧化物前期药物的抗癌疗效在体外和体内进行评估.
主要方法:
- 氧化预药物的合成和表征.
- 通过X射线辐射生成的水合电子的N氧化物减少的体外研究.
- 细胞研究评估辐射激活前药物的疗效.
- 在体实验中评估N-氧化物前药物在放射治疗后的治疗效果和瘤选择性.
主要成果:
- 在溶液和活细胞中由X射线辐射产生的水合电子 (e-aq) 有效地减少了N氧化物.
- 结构-活性关系选揭示了电子介导的N-氧化物减少的机制.
- 一种基于坎普托素 (CPT) 的N-氧化原药在放射治疗时表现出强烈的抗癌活性.
- 该策略显示了瘤选择性激活和有效性,最大限度地减少了全身暴露.
结论:
- 用X射线诱导的化学方法为激活N-氧化物前药物提供了精确和有效的方法.
- 这种新型的放射治疗激活前药物策略对癌症治疗具有重大临床意义.
- 这种方法可以为辐射诱导的癌症疗法设计多功能前药物,可能使超过50%的接受放射治疗的癌症患者受益.
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