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Rudolph Virchow discovered spindle-shaped cells called fibroblasts in 1858. Inactive fibroblasts, called fibrocytes, become activated by various stimuli, such as growth factors and inflammatory cytokines. Activated fibroblasts play a crucial role in wound healing, inflammation, formation of new blood vessels, and cancer progression. Uncontrolled activation of fibroblasts results in fibrosis, the excess deposition of fibrous tissue, which can lead to scarring and affect normal organs. This...
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机器学习信息化纳米联合组装抑制纤维细胞激活蛋白,并改善纤维化组织中的药物递送.

Zehua Liu1,2, Qiang Long3, Yihao Liu4

  • 1Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.

Advanced materials (Deerfield Beach, Fla.)
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概括

我们使用SP-13786 (SP) 助剂开发了稳定的纳米粒子 (SCAN),以改善药物输送. 在纤维性疾病中,SCAN增强了药物积累和治疗疗效.

关键词:
纤维细胞激活蛋白的激活蛋白.心肌再输血损伤的伤害胰腺瘤是一种瘤.定量结构-财产分析.响应式的药物输送方式自组装的纳米粒子.

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科学领域:

  • 生物医学工程 生物医学工程
  • 纳米医学是一种纳米医学.
  • 药物输送系统 药物输送系统

背景情况:

  • 基于纳米粒子的药物输送面临着制造和积累方面的挑战.
  • 纤维性疾病阻碍了药物透和治疗效果.
  • 纤维细胞激活蛋白 (FAP) 是纤维状况中的一个目标.

研究的目的:

  • 引入SP-13786 (SP) 作为一种通用辅助剂,用于用疏水药物制造稳定的纳米粒子 (SCAN).
  • 通过模拟和可解释机器学习 (XML) 来研究SCAN的组装机制.
  • 评估SCAN在纤维化疾病模型中的治疗潜力.

主要方法:

  • SP-13786与疏水药物的共同沉形成了SCAN.
  • 复合查 (861名候选人) 以确定SP作为有效的辅助剂.
  • 计算模拟和可解释的机器学习 (XML) 用于分析SCAN组件.
  • 在FAP阳性细胞和疾病模型中的体外和体内生物评估.

主要成果:

  • SP显著提高了各种疏水性药物的体稳定性和药物负载.
  • SCAN组件由平衡的芳香度,刚性和介导的相互作用来控制.
  • 在FAP阳性细胞中,SCAN改善了药物递送和疗效.
  • SCAN减弱了纤维化诱导的药物透障碍,增加了纤维化组织中的药物积累.
  • 在渐进性纤维化模型中,SCAN的增强生物可用性与卓越的治疗结果相关.

结论:

  • SP-13786是一种多功能辅助剂,可通过易于共同沉开发稳定的纳米粒子 (SCAN).
  • XML为SCAN组装提供了机械的洞察力,使得合理的纳米医药设计成为可能.
  • SCAN代表了一种有前途的纳米治疗平台,用于治疗有病理性纤维化和药物输送受损的疾病.