针对瘤微环境的癌症治疗的微RNA沉默
Christopher J Cheng1, Raman Bahal2, Imran A Babar3
11] Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06511, USA [2] Department of Biomedical Engineering, Yale University, New Haven, Connecticut 06511, USA [3] Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06511, USA.
Nature
|November 20, 2014
概括
研究人员开发了一种针对酸性瘤微环境的抗miRs (反意义寡合物) 的新型输送平台. 这个平台在小鼠淋巴瘤模型中有效地抑制瘤反应因子,为向癌症药物输送提供了一个新的策略.
科学领域:
- 分子生物学分子生物学
- 在瘤学瘤学.
- 药物运输 药物运输 药物运输
背景情况:
- 微RNAs调节基因表达,并在生物过程中至关重要.
- 失调的microRNAs,特别是oncomiRs,与癌症的发展有关.
- 目前的抗miR疗法面临着在体内向瘤细胞输送的挑战.
研究的目的:
- 引入一种针对酸性瘤微环境的新型抗miR输送平台.
- 克服阻碍当前抗miR疗效的生理和细胞障碍.
- 调查酸核酸抗米Rs与pHLIP结合的酸核酸抗米Rs在癌症治疗中的潜力.
主要方法:
- 核酸抗米Rs与pH敏感 (pHLIP) 的结合.
- 对构造物向酸性瘤微环境 (pH ~6) 的能力的评估.
- 评估通过非内细胞通路进入细胞.
- 在小鼠淋巴瘤模型中测试miR-155 oncomiR的抑制.
主要成果:
- 这种新的pHLIP-antimiR构造成功地准了酸性瘤微环境.
- 该平台在酸性条件下促进了抗miR在等离子体膜中的传输.
- 在小鼠淋巴瘤模型中观察到有效抑制miR-155科米R.
结论:
- 开发的antimiR输送平台显示了针对性癌症治疗的前景.
- 这种方法克服了关键的交付障碍,提供了一种新的瘤瘤抑制策略.
- 这项研究为抗miRs作为抗癌药物提出了一个新的模型,对药物输送有广泛的影响.
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