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Optimizing the Size of Micellar Nanoparticles for Efficient siRNA Delivery

机译：优化胶束纳米颗粒的大小，以有效地传递siRNA

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摘要

Delivery of small interfering RNA (siRNA) by nanocarriers has shown promising therapeutic potential in cancer therapy. However, poor understanding of the correlation between the physicochemical properties of nanocarriers and their interactions with biological systems has significantly hindered its anticancer efficacy. Herein, in order to identify the optimal size of nanocarriers for siRNA delivery, different sized cationic micellar nanoparticles (MNPs) (40, 90, 130, and 180 nm) are developed that exhibit similar siRNA binding efficacies, shapes, surface charges, and surface chemistries (PEGylation) to ensure size is the only variable. Size-dependent biological effects are carefully and comprehensively evaluated through both in vitro and in vivo experiments. Among these nanocarriers, the 90 nm MNPs show the optimal balance of prolonged circulation and cellular uptake by tumor cells, which result in the highest retention in tumor cells. In contrast, larger MNPs are rapidly cleared from the circulation and smaller MNPs are inefficiently taken up by tumor cells. Accordingly, 90 nm MNPs carrying polo-like kinase 1 (Plk1)-specific siRNA (siPlk1) show superior antitumor efficacy, indicating that 90 nm could either be the optimal size for systemic delivery of siRNA or close to it. Our findings provide valuable information for rationally designing nanocarriers for siRNA-based cancer therapy in the future.
机译：通过纳米载体递送小干扰RNA（siRNA）已显示出在癌症治疗中有希望的治疗潜力。然而，对纳米载体的物理化学性质及其与生物系统相互作用之间的相关性的了解不足，严重阻碍了其抗癌功效。在本文中，为了确定用于siRNA输送的纳米载体的最佳尺寸，开发了不同尺寸的阳离子胶束纳米颗粒（MNP）（40、90、130和180 nm），它们表现出相似的siRNA结合效率，形状，表面电荷和表面化学（PEG化）以确保大小是唯一变量。通过体外和体内实验，仔细，全面地评估了大小相关的生物学效应。在这些纳米载体中，90 nm MNPs表现出肿瘤细胞延长循环和细胞摄取的最佳平衡，从而导致在肿瘤细胞中的保留率最高。相反，较大的MNP从循环中迅速清除，较小的MNP被肿瘤细胞吸收不足。因此，携带polo样激酶1（Plk1）特异性siRNA（siPlk1）的90 nm MNP显示出优异的抗肿瘤功效，表明90 nm可能是siRNA全身递送的最佳大小或接近它。我们的发现为将来为基于siRNA的癌症治疗合理设计纳米载体提供了有价值的信息。

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  • 来源
    《Advanced Functional Materials》 |2015年第30期|4778-4787|共10页
  • 作者

    Liang Shi; Yang Xian-Zhu; Du Xiao-Jiao; Wang Hong-Xia; Li Hong-Jun; Liu Wei-Wei; Yao Yan-Dan; Zhu Yan-Hua; Ma Yin-Chu; Wang Jun; Song Er-Wei;

  • 作者单位

    Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Breast Tumor Ctr, Guangzhou 510120, Guangdong, Peoples R China;

    Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China|Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China|Hefei Univ Technol, Sch Med Engn, Dept Med Mat & Rehabil Engn, Hefei 230009, Anhui, Peoples R China;

    Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China|Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China;

    Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China|Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China;

    Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China|Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China;

    Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China|Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China;

    Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Breast Tumor Ctr, Guangzhou 510120, Guangdong, Peoples R China;

    Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China|Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China;

    Hefei Univ Technol, Sch Med Engn, Dept Med Mat & Rehabil Engn, Hefei 230009, Anhui, Peoples R China;

    Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China|Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China|Univ Sci & Technol China, Sch Life Sci, CAS Key Lab Innate Immun & Chron Dis, Hefei 230027, Anhui, Peoples R China|Univ Sci & Technol China, Med Ctr, Hefei 230027, Anhui, Peoples R China;

    Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Breast Tumor Ctr, Guangzhou 510120, Guangdong, Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    cancer therapy; drug delivery; nanocarriers; siRNA; size effect;

    机译：癌症治疗;药物输送;纳米载体;siRNA;大小效应;

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