控制药物输送的酶响应Zr基金属有机框架:利用可点击的PEG-酸盐配体
Carolina Carrillo-Carrión1, Valentine Comaills2, Ana M Visiga1
1Institute for Chemical Research (IIQ), CSIC-University of Seville, 41092 Sevilla, Spain.
ACS applied materials & interfaces
|May 30, 2023
概括
我们开发了一种新的纳米金属有机框架 (MOF),用于控制药物输送. 这种MOF在响应性酸酶 (ALP) 酶活性时释放多克索鲁比,显示了针对性癌症治疗的前景.
科学领域:
- 材料科学 材料科学 材料科学
- 纳米技术纳米技术
- 生物医学工程 生物医学工程
背景情况:
- 金属有机框架 (MOF) 为药物输送应用提供可调节的特性.
- 控制释放机制对于提高治疗疗效和减少副作用至关重要.
- 酶响应系统是针对特定细胞环境的向药物递送的有希望的策略.
研究的目的:
- 开发一种基于纳米级Zr的MOF (UiO-66),能够控制药物释放.
- 用N3-PEG-PO3配体对UiO-66进行功能化,以提高稳定性,成像性和刺激反应性.
- 为了研究由性酸酶 (ALP) 活性触发的多克索鲁比的选择性释放.
主要方法:
- 功能化的UiO-66 MOFs的合成和表征.
- 在体外研究以评估含酸盐介质中的合体稳定性.
- 对多克索鲁比释放动学的评估,以应对不同的ALP度.
- 使用不同ALP基因表达水平的癌细胞系 (HeLa,MDA-MB-231,MCF7) 的细胞研究.
- 对潜在的成像剂附件进行点击化学.
主要成果:
- 功能化的UiO-66 (N3-(PEG) 20-PO3) 显示出更好的体稳定性.
- 该MOF表现出ALP触发的,可控释放的多克索鲁比辛.
- 在具有更高ALP基因表达 (HeLa) 的细胞系中观察到增强的多克索鲁比辛释放.
- 与裸体MOF相比,功能化MOF的细胞内稳定性得到了改善.
结论:
- 功能化N3-PEG-PO3的UiO-66 MOF可以在对ALP的反应中控制多克索鲁比辛的释放.
- 该系统展示了在癌症治疗中向药物递送的潜力,利用差异ALP表达.
- 功能化战略为开发多功能,刺激响应的纳米载体提供了一个平台.
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