通过阳离子生物聚合物共释放的siRNA和药物的增强抗癌活性:克服静电排斥
1Pharmaceutics & Pharmacokinetics Division, Council of Scientific & Industrial Research-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow, Uttar Pradesh, 226031, India.
Nanomedicine (London, England)
|July 28, 2023
概括
研究人员使用改性氨酸开发了纳米粒子,将多克索鲁比和siRNA输送到结肠癌细胞中. 这种方法实现了显著的基因和蛋白质下调,证明了癌症治疗的有效代码传递.
科学领域:
- 生物技术是生物技术.
- 纳米医学是一种纳米医学.
- 在瘤学瘤学.
背景情况:
- 氨酸 (HA) 是细胞外基质的关键组成部分,在癌症进展中至关重要.
- 修改后的HA可以被设计为向药物和基因传递.
- 在许多癌症中,CD44受体过度表达,包括HT-29结肠癌细胞,使其成为治疗的目标.
研究的目的:
- 将多克索鲁比辛 (抗癌药物) 和siRNA (基因沉默剂) 代引入CD44过度表达HT-29结肠癌细胞.
- 用一种基于改性氨酸 (6-O-[3-hexadecyloxy-2-hydroxypropyl]-氨酸) 的阳离子,两性生物聚合物作为纳米载体.
- 评估这种纳米载体系统在向癌症治疗中的有效性.
主要方法:
- 使用动态光散射,扫描电子显微镜和传输电子显微镜进行纳米粒子表征.
- 分子对接用于预测组件之间的相互作用.
- 在体外研究包括药物释放,凝电泳,基因沉默试验和西部斑点分析.
主要成果:
- 成功形成能够共释放多克索鲁比和siRNA的纳米颗粒.
- 通过 western blot 实现了 69% 的目标基因倒置和 5.7 倍的目标蛋白质下调.
- 证明了结合和疏水性相互作用克服了siRNA和改性HA载体之间的排斥力.
结论:
- 开发的改性氨酸基纳米颗粒有效地将doxorubicin和siRNA转化为HT-29结肠癌细胞.
- 该系统显示了针对性基因沉默和癌症治疗中药物输送的巨大潜力.
- 这项研究突出了离子载体在药物和siRNA同时输送方面的成功应用.
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