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首页> 外文期刊>Biomaterials Science >Solvent-driven, self-assembled acid-responsive poly(ketalized serine)/siRNA complexes for RNA interference
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Solvent-driven, self-assembled acid-responsive poly(ketalized serine)/siRNA complexes for RNA interference

机译：用于RNA干扰的溶剂驱动的自组装酸响应性聚（酮化丝氨酸）/ siRNA复合物

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摘要

Advances in bionanotechnology aim to develop smart nucleic acid delivery carriers with stimuli-responsive features to overcome challenges such as non-biodegradability, rapid clearance, immune response, and reaching intracellular targets. Peptide-based nanomaterials have become widely used in the field of gene and drug delivery due to their structural versatility and biomimetic properties. Particularly, polypeptide gene vectors that respond to biological stimuli, such as acidic intracellular environments, have promising applications in mediating efficient endosomal escape and drug release. Unfortunately, synthesis strategies for efficient polymerization of acid-labile peptides have been limited due to conditions that fail to preserve acid-degradable functional groups. Stable urethane derivatives of the acid-labile amino acid ketalized serine (kSer) were synthesized and polymerized to a high molecular weight under permissive conditions independent of elevated temperature, restrictive solvents, or an inert atmosphere. A new formulation strategy utilizing solvent-driven self-assembly of poly(kSer) peptides with small interfering RNA (siRNA) was developed, and the resulting poly(kSer)/siRNA complexes were further cross-linked for reinforced stability under physiological conditions. The complexes were highly monodisperse and precisely spherical in morphology, which has significant clinical implications in definitive biodistribution, cellular internalization, and intracellular trafficking patterns. Self-assembled, cross-linked poly(kSer)/siRNA complexes demonstrated efficient nucleic acid encapsulation, internalization, endosomal escape, and acid-triggered cargo release, tackling multiple hurdles in siRNA delivery. The acid-responsive polypeptides and solvent-driven self-assembly strategies demonstrated in this study could be applicable to developing other efficient and safe delivery systems for gene and drug delivery.
机译：Bionanootechnology的进步旨在开发具有刺激响应特征的智能核酸输送载体，以克服诸如非生物降解性，快速间隙，免疫应答以及到达细胞内靶标的挑战。由于其结构多种性和仿生性能，基于肽的纳米材料已广泛用于基因和药物递送领域。特别地，对生物刺激的多肽基因载体，例如酸性细胞内环境，在介导有效的内体逃逸和药物释放方面具有希望的应用。遗憾的是，由于未能保持耐酸可降解的官能团的条件，酸性不稳定肽的有效聚合的合成策略受到限制。合成酸性稳定氨基酸胺化丝氨酸丝氨酸（Kser）的稳定氨基甲酸酯衍生物，并在允许的允许条件下聚合到高分子量，与升高的温度，限制性溶剂或惰性气氛无关。利用具有小干扰RNA（siRNA）的溶剂驱动自组装的新的配方策略进行了小干扰RNA（siRNA），并在生理条件下进一步交联以加强稳定性的交联。复合物在形态学中具有高度单分散，精确球形，具有明确的生物分布，细胞内化和细胞内贩运模式具有显着的临床意义。自组装，交联聚（KSER）/ siRNA复合物证明了有效的核酸包封，内化，内体逸出和酸触发的货物释放，在siRNA递送中解决多个障碍。本研究证明的酸性响应多肽和溶剂驱动的自组装策略可适用于开发用于基因和药物递送的其他有效和安全的递送系统。

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  • 来源
    《Biomaterials Science》 |2020年第23期|共12页
  • 作者

    Wong Shirley; Kemp Jessica A.; Shim Min Suk; Kwon Young Jik;

  • 作者单位

    Univ Calif Irvine Sch Pharm &

    Pharmaceut Sci Dept Pharmaceut Sci Irvine CA 92697 USA;

    Univ Calif Irvine Sch Pharm &

    Pharmaceut Sci Dept Pharmaceut Sci Irvine CA 92697 USA;

    Incheon Natl Univ Div Bioengn Incheon 22012 South Korea;

    Univ Calif Irvine Sch Pharm &

    Pharmaceut Sci Dept Pharmaceut Sci Irvine CA 92697 USA;

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  • 正文语种 eng
  • 中图分类 分子生物学;
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