• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Advanced Functional Materials >Photocrosslinked Bioreducible Polymeric Nanoparticles for Enhanced Systemic siRNA Delivery as Cancer Therapy
【24h】

Photocrosslinked Bioreducible Polymeric Nanoparticles for Enhanced Systemic siRNA Delivery as Cancer Therapy

机译：Photocrosslind的生物生产聚合物纳米颗粒，用于增强全身siRNA递送作为癌症治疗

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Clinical translation of polymer-based nanocarriers for systemic delivery of RNA has been limited due to poor colloidal stability in the blood stream and intracellular delivery of the RNA to the cytosol. To address these limitations, this study reports a new strategy incorporating photocrosslinking of bioreducible nanoparticles for improved stability extracellularly and rapid release of RNA intracellularly. In this design, the polymeric nanocarriers contain ester bonds for hydrolytic degradation and disulfide bonds for environmentally triggered small interfering RNA (siRNA) release in the cytosol. These photocrosslinked bioreducible nanoparticles (XbNPs) have a shielded surface charge, reduced adsorption of serum proteins, and enable superior siRNA-mediated knockdown in both glioma and melanoma cells in high-serum conditions compared to non-crosslinked formulations. Mechanistically, XbNPs promote cellular uptake and the presence of secondary and tertiary amines enables efficient endosomal escape. Following systemic administration, XbNPs facilitate targeting of cancer cells and tissue-mediated siRNA delivery beyond the liver, unlike conventional nanoparticle-based delivery. These attributes of XbNPs facilitate robust siRNA-mediated knockdown in vivo in melanoma tumors colonized in the lungs following systemic administration. Thus, biodegradable polymeric nanoparticles, via photocrosslinking, demonstrate extended colloidal stability and efficient delivery of RNA therapeutics under physiological conditions, and thereby potentially advance systemic delivery technologies for nucleic acid-based therapeutics.
机译：基于聚合物的纳米载波的临床翻译是由于血液流中的胶体稳定性差和RNA细胞内递送到胞浆溶质的临床翻译。为了解决这些限制，本研究报告了一种新的策略，该策略包括生物化纳米颗粒的光源型纳米粒子，以改善稳定性和快速释放RNA的RNA细胞内。在该设计中，聚合物纳米载体含有用于水解劣化和用于环境触发的小干扰RNA（siRNA）释放在胞浆溶胶中的酯键和二硫键。这些光电解的生物能力纳米颗粒（XbnPS）具有屏蔽表面电荷，降低血清蛋白的吸附，并使与非交联制剂相比，高血清条件下的胶质瘤和黑素瘤细胞中的优异siRNA介导的敲低。机械地，Xbnps促进细胞吸收和二级和叔胺的存在使得能够有效的内体逃逸。与常规的纳米颗粒类递送不同，XbNPS促进XbNPS促进癌细胞和组织介导的siRNA递送超过肝脏。 XBNPS的这些属性促进了在全身给药后肺部殖民化的黑色素瘤肿瘤中体内体内鲁棒的siRNA介导的敲低。因此，可生物降解的聚合物纳米颗粒通过光源瘤，在生理条件下表现出延长的胶体稳定性和高效递送RNA治疗剂，从而潜在地推进基于核酸的治疗剂的系统输送技术。

著录项

  • 来源
    《Advanced Functional Materials》 |2021年第17期|2009768.1-2009768.17|共17页
  • 作者

    Karlsson Johan; Tzeng Stephany Y.; Hemmati Shayan; Luly Kathryn M.; Choi Olivia; Rui Yuan; Wilson David R.; Kozielski Kristen L.; Quinones-Hinojosa Alfredo; Green Jordan J.;

  • 作者单位

    Johns Hopkins Univ Sch Med Dept Biomed Engn Baltimore MD 21231 USA|Uppsala Univ Dept Chem Angstrom Lab SE-75121 Uppsala Sweden;

    Johns Hopkins Univ Sch Med Dept Biomed Engn Baltimore MD 21231 USA;

    Johns Hopkins Univ Sch Med Dept Biomed Engn Baltimore MD 21231 USA;

    Johns Hopkins Univ Sch Med Dept Biomed Engn Baltimore MD 21231 USA;

    Johns Hopkins Univ Sch Med Dept Biomed Engn Baltimore MD 21231 USA;

    Johns Hopkins Univ Sch Med Dept Biomed Engn Baltimore MD 21231 USA;

    Johns Hopkins Univ Sch Med Dept Biomed Engn Baltimore MD 21231 USA;

    Johns Hopkins Univ Sch Med Dept Biomed Engn Baltimore MD 21231 USA|Karlsruhe Inst Technol Inst Funct Interfaces D-76344 Eggenstein Leopoldshafen Germany;

    Mayo Clin Florida Dept Neurosurg Jacksonville FL 32224 USA;

    Johns Hopkins Univ Sch Med Dept Biomed Engn Baltimore MD 21231 USA|Johns Hopkins Univ Bloomberg Kimmel Inst Canc Immunotherapy Sidney Kimmel Comprehens Canc Ctr Sch Med Dept Mat Sci & Engn Baltimore MD 21231 USA|Johns Hopkins Univ Bloomberg Kimmel Inst Canc Immunotherapy Sidney Kimmel Comprehens Canc Ctr Sch Med Dept Neurosurg Baltimore MD 21231 USA|Johns Hopkins Univ Bloomberg Kimmel Inst Canc Immunotherapy Sidney Kimmel Comprehens Canc Ctr Sch Med Dept Oncol Baltimore MD 21231 USA|Johns Hopkins Univ Bloomberg Kimmel Inst Canc Immunotherapy Sidney Kimmel Comprehens Canc Ctr Sch Med Dept Ophthalmol Baltimore MD 21231 USA|Johns Hopkins Univ Bloomberg Kimmel Inst Canc Immunotherapy Sidney Kimmel Comprehens Canc Ctr Sch Med Dept Chem & Biomol Engn Baltimore MD 21231 USA;

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

    bioreducible; crosslinking; nanoparticles; siRNA; stimuli#8208; responsive polymers;

    机译：生物的;交联;纳米颗粒;siRNA;刺激＆＃8208;响应聚合物;

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号