基于碎片的药物纳米聚合揭示了自我组装的驱动因素
Chen Chen1,2,3, You Wu1,2,3, Shih-Ting Wang4
1Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Nature communications
|December 14, 2023
概括
了解药物纳米聚合物形成是关键. 芳香组和键驱动自我组装,使药物输送的合理设计和克服查挑战成为可能.
科学领域:
- 药用化学 医学化学
- 材料科学 材料科学 材料科学
- 纳米技术纳米技术
背景情况:
- 药物纳米聚合物可以在查中产生虚假阳性或改善药物输送的药理动力学.
- 由于未知的结构驱动因素,预测细胞内聚合和设计纳米聚合物载体仍然具有挑战性.
研究的目的:
- 用小分子碎片研究纳米聚合物的自我组装机制.
- 为了确定推动纳米聚合物形成的关键分子力量.
- 为了实现基于纳米聚合物的药物输送系统的合理设计.
主要方法:
- 使用小分子碎片研究纳米聚合物的自我组装.
- 应用结构组装关系分析对药物索拉费尼布.
- 分析了有助于自我组装的分子力量,包括芳香相互作用和键.
主要成果:
- 芳香基和键接受器/捐赠器对于纳米聚合物形成至关重要.
- π-π堆叠和键被确定为纳米聚合的关键驱动因素.
- 纳米聚合物形成可以从药物碎片的基结构中预测,正如在 sorafenib.
- 药物纳米聚合物表现出稳定的无形核心外结构.
结论:
- 理性设计原则可以应用于控制细胞内聚合.
- 这些发现解决了药物输送和传统/基于片段的药物开发的挑战.
- 了解自我组装机制对于优化药物特性和治疗应用至关重要.
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