瘤微环境激活的氧酸盐在现场合成,用于增强化学动力学治疗
Bowen Li1, Chongzhi Wu2,3, Zhiyao Li2,3
1Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, 117585Singapore.
ACS nano
|September 19, 2024
概括
这项研究引入了一种新型纳米药物,用于增强化学动力学疗法 (CDT),通过产生过氧酸盐 (ONOO−),克服基 (·OH) 在癌症治疗中的产生局限性.
科学领域:
- 生物医学工程 生物医学工程
- 纳米技术 纳米技术
- 癌症治疗 癌症治疗
背景情况:
- 化学动力学疗法 (CDT) 利用基基 (·OH) 导致癌细胞死亡,比传统治疗方法提供优势,如克服药物耐药性和减少副作用.
- 临床CDT面临的挑战是由于OH生成不足及其短暂的体内寿命.
- 开发新型纳米药物对于提高CDT的有效性和克服当前的局限性至关重要.
研究的目的:
- 开发一种基于过氧酸盐 (ONOO−) 的纳米药物,用于增强化学动力学疗法 (CDT).
- 改善活性氧物种 (ROS) 的生成,克服癌症治疗中OH的局限性.
- 创造一种瘤向纳米药物,具有增强的治疗效果和生物安全性.
主要方法:
- 使用MOF-199,NO供体 (PArg) 和多克索鲁比辛 (DOX) 作为NOX4激活剂制造一个纳米药物 (DOX@PMOF).
- 利用癌细胞的谷氨酸 (GSH) 来降低MOF-199到Cu+,通过芬顿式反应产生OH.
- 用释放的DOX调节NOX4表达,以增加H2O2水平,进一步促进OH生成.
- 在现场通过NO (来自PArg) 和OH的反应合成ONOO−.
- 用同类细胞膜涂层DOX@MPMOF,以创建瘤向纳米药物 (DOX@MPMOF).
主要成果:
- 在癌细胞内,DOX@PMOF有效地产生OH,随后产生ONOO.
- NO和OH的联合作用导致ONOO−的形成,它比OH具有更高的毒性和更长的寿命.
- DOX@MPMOF在体内显示出显著抑制瘤生长和转移.
- 开发的纳米药物表现出良好的生物安全性.
结论:
- 开发的基于过氧化物 (ONOO−) 的纳米药物 (DOX@PMOF) 通过产生更强的活性物种,有效地增强了化学动力学疗法.
- 瘤向纳米药物 (DOX@MPMOF) 在抑制瘤生长和转移方面显示出有前途的治疗潜力,具有良好的生物安全性.
- 这种方法提供了一个有希望的策略,以克服传统CDT的局限性,并改善癌症治疗结果.
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