针对癌细胞下调的酶指导组装和拆卸过程
Zhaoqianqi Feng1, Huaimin Wang1, Rong Zhou1
1Department of Chemistry, Brandeis University , 415 South Street, Waltham, Massachusetts 02454, United States.
Journal of the American Chemical Society
|March 4, 2017
概括
这项研究引入了一种针对癌细胞功能丧失的新型化疗策略. 由酶指导的前体的组装和拆卸通过利用下调酶选择性地抑制癌细胞.
科学领域:
- 生物化学
- 纳米技术
- 癌症学
背景情况:
- 与正常细胞相比,癌细胞表现出上调 (功能增加) 和下调 (功能丧失) 的途径.
- 在化疗中向癌细胞的功能增长是常见的,但向功能丧失仍然是一个重大挑战.
- 为了有效治疗癌症,开发新的治疗策略对抗癌细胞的降低调节至关重要.
研究的目的:
- 开发一种新的化疗方法,利用酶指导组装和拆卸来降低癌细胞的调节.
- 设计可作为碳酸酶 (CES) 和酸酶 (ALP) 的基质的基前体.
- 为了证明选择性抑制癌细胞与下调ES活动.
主要方法:
- 能够通过CES和ALP进行裂变的前体的设计.
- 使用ALP诱导前体自组合成纳米纤维.
- 使用CES触发纳米纤维的拆卸.
- 在具有差异性CES表达的癌细胞 (OVSAHO) 和正常细胞 (HepG2) 上测试前体的选择性.
主要成果:
- 在ALP脱后,前体自组合成纳米纤维.
- 这些纳米纤维因CES催化而分裂.
- 设计的前体选择性地抑制了下调CES活性的癌细胞 (OVSAHO).
- 这些前体对过度表达CES (HepG2) 的肝细胞无害,尽管具有相似的ALP活性.
结论:
- 这项研究提出了针对癌细胞功能丧失的潜在化疗策略 (降低调节).
- 酶指导组装和拆卸的组合为选择性向癌细胞提供了一种新方法.
- 这种方法突显了利用低调细胞功能来治疗癌症的潜力.
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