在结合RNAi和基抗癌剂时最大限度地发挥协同作用
Haihua Xiao1, Ruogu Qi1, Ting Li1
1Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
(II) 抗癌剂迅速化siRNA,降低RNA干扰 (RNAi) 的效率. 一种新型的细胞策略,可同时提供白金 (IV) 和siRNA,最大限度地抑制BCL-2mRNA并增强抗癌作用.
科学领域:
- 生物化学和分子生物学
- 纳米技术在医学上
- 癌症治疗方法
背景情况:
- 与基化疗相结合的RNA干扰 (RNAi) 面临由于引起的siRNA损伤的挑战.
- 在典型的实验度下, (II) 剂在siRNA中与瓜诺辛残留物形成添加物,从而降低RNAi的有效性.
- (IV) 类似物避免了直接的siRNA化,但显示细胞吸收和功效较低.
研究的目的:
- 研究 (II) 剂对siRNA完整性和RNAi效率的影响.
- 开发和评估一种用于RNAi和化疗的新药输送系统.
- 优化BCL-2siRNA和类型的协同交付,以改善癌症治疗.
主要方法:
- 分析-siRNA附加物形成的光谱表征.
- 开发可生物降解的mPEG-b-PCL-b-PLL微粒,同时提供siRNA和剂.
- 在体外评估BCL- 2mRNA抑制,细胞内含量,DNA附加物形成,亡诱导和抗增殖活性.
主要成果:
- (II) 剂迅速化BCL-2 siRNA,显著降低其抑制mRNA水平的能力.
- 在细胞中同时封装BCL- 2 siRNA和类型,达到最大的BCL- 2 mRNA抑制 (<10%).
- 细胞策略增强了细胞内白金水平 (~4倍),DNA添加 (>5倍),亡 (~4倍) 和抗增殖活性 (10-100倍).
结论:
- 在组合疗法中, (II) 剂的标准度对siRNA功能有害.
- 基于和siRNA的共递系统是协同治疗癌症的有希望的策略.
- 这种可通用的方法可以最大限度地提高RNAi和基剂之间的协同作用,用于治疗应用和药物查.
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