酸作为抗癌药物
Felicity F Noakes1,2, Kirsty L Smitten1,3, Laura E C Maple2
1Department of Chemistry, The University of Sheffield, Western Bank, Sheffield S3 7HF, U.K.
两种新型的多聚基有机显示出选择性癌细胞毒性和增强的光活性. 在纳米分子度下,更活跃的阳离子会诱导溶解体依赖的细胞死亡,对动物有最小的毒性.
科学领域:
- 医学化学
- 摄影化学
- 细胞生物学
背景情况:
- 聚烯化合物是光活性金属复合物的多功能联体.
- 研究它们的生物特性对于治疗应用至关重要.
- 了解结构活动关系指导新型药物的设计.
研究的目的:
- 研究两种水溶性聚烯基有机的生物特性和治疗潜力.
- 评估它们的细胞毒性,细胞吸收和作用机制.
- 在动物模型中评估它们的初步毒性.
主要方法:
- 通过各种细胞系进行细胞毒性查.
- 使用内在发光的细胞吸收研究.
- 聚焦显微镜和刺激辐射耗尽 (STED) 纳米镜.
- 传输电子显微镜 (TEM) 用于超结构分析.
- 菌毒性测定
主要成果:
- 这两种阴离子对癌细胞和HEK293细胞具有选择性细胞毒性.
- 在可见光照射时,较长的阴离子显示出增强的光活性,在纳米度下诱导细胞死亡.
- 细胞吸收研究揭示了更喜欢脂肪的子的偏好内部化.
- 治疗导致了溶酶体胀,线粒体功能障碍和溶酶体依赖细胞死亡 (死亡和细胞亡).
- 在高达80mg/kg的Galleria菌模型中没有发现可检测的毒性.
结论:
- 聚甲基有机酸是治疗开发的有前途的光活性化合物.
- 活性体具有强烈的光激活细胞毒性,具有良好的初步安全性.
- 需要进一步的研究来探索它们的治疗效果和优化它们的设计.
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