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首页> 外文期刊>Biomaterials Science >Effective systemic siRNA delivery using dual-layer protected long-circulating nanohydrogel containing an inorganic core
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Effective systemic siRNA delivery using dual-layer protected long-circulating nanohydrogel containing an inorganic core

机译：使用双层保护长循环纳米水凝胶的有效全身siRNA递送含有无机核心

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摘要

Systemic delivery of small interfering RNA (siRNA) has been mainly impeded by enzymatic degradation and poor cellular uptake. Calcium phosphate (CaP) has been considered a potential candidate for siRNA delivery because of its excellent biocompatibility and capability of entrapping siRNA in the crystal core. Based on the property of 3,4-dihydroxy-l-phenylalanine (dopa) binding to the surface of the CaP crystal, dual hydrogel layers consisting of a macromolecular dextran (dex) and polyethylene glycol (PEG) were introduced on the surface of the inorganic CaP core for prolonged circulation. Dextran conjugated with dopa and polyethylene glycol (PEG) (PEG-dex-dopa) can effectively control the overgrowth of the CaP/siRNA core and stabilize it by dual electrically neutral hydrophilic layers of dextran and PEG, which additionally provide reduced hepatic accumulation and systemic clearance. The dual shield of PEG-dex-dopa nanohydrogel containing a CaP/siRNA core (PEG-dex-dopa/CaP/siRNA) significantly improved the pharmacokinetic behaviors of siRNA after systemic administration, resulting in its increased distribution to tumors and the effective inhibition of tumor growth by silencing vascular endothelial growth factor (VEGF) gene expression through the enhanced permeability and retention (EPR) effect.
机译：通过酶促降解和细胞摄取不良，主要迁移小干扰RNA（siRNA）。磷酸钙（帽）被认为是siRNA递送的潜在候选者，因为它具有优异的生物相容性和夹在晶体中的siRNA的能力。基于与帽晶体表面结合的3,4-二羟基-1-苯丙氨酸（DOPA）的性质，在表面表面上引入了由大分子葡聚糖（DEX）和聚乙二醇（PEG）组成的双水凝胶层。无机帽核心长期循环。与DOPA和聚乙二醇（PEG）（PEG-DEX-DOPA）缀合的葡聚糖可以有效地控制帽/ siRNA核的过度生长，并通过双电中性亲水层的葡聚糖和PEG稳定，其另外提供降低的肝积聚和系统性清除。含有帽/ siRNA核心（PEG-DEX-DOPA /帽/ siRNA）的PEG-DEX-DOPA纳米水凝胶的双屏蔽显着改善了SIRNA后SIRNA的药代动力学行为，导致其对肿瘤的分布增加和有效抑制通过沉默血管内皮生长因子（VEGF）基因表达通过增强的渗透率和保留（EPR）效应来肿瘤生长。

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  • 来源
    《Biomaterials Science》 |2019年第8期|共10页
  • 作者

    Yin Yue; Lee Min Sang; Lee Jung Eun; Lim Su Yeon; Kim E. Seul; Jeong Jaeback; Kim Dahwun; Kim Jaeyun; Lee Doo Sung; Jeong Ji Hoon;

  • 作者单位

    Sungkyunkwan Univ Sch Pharm Theranost Macromol Res Ctr Suwon 440746 South Korea;

    Sungkyunkwan Univ Sch Pharm Theranost Macromol Res Ctr Suwon 440746 South Korea;

    Sungkyunkwan Univ Sch Pharm Theranost Macromol Res Ctr Suwon 440746 South Korea;

    Sungkyunkwan Univ Sch Pharm Theranost Macromol Res Ctr Suwon 440746 South Korea;

    Sungkyunkwan Univ Sch Pharm Theranost Macromol Res Ctr Suwon 440746 South Korea;

    Sungkyunkwan Univ Sch Pharm Theranost Macromol Res Ctr Suwon 440746 South Korea;

    Sungkyunkwan Univ Sch Pharm Theranost Macromol Res Ctr Suwon 440746 South Korea;

    Sungkyunkwan Univ Sch Chem Engn Theranost Macromol Res Ctr Suwon 440746 South Korea;

    Sungkyunkwan Univ Sch Chem Engn Theranost Macromol Res Ctr Suwon 440746 South Korea;

    Sungkyunkwan Univ Sch Pharm Theranost Macromol Res Ctr Suwon 440746 South Korea;

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  • 正文语种 eng
  • 中图分类 分子生物学;
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