Non-viral Delivery of Nucleic Acids: Insight Into Mechanisms of Overcoming Intracellular Barriers.
Non-viral Delivery of Nucleic Acids: Insight Into Mechanisms of Overcoming Intracellular Barriers.
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DOI：
10.3389/fphar.2018.00971
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发表时间：
2018
影响因子：
5.6
通讯作者：
Reineke J
中科院分区：
文献类型：
--
作者：
Durymanov M;Reineke J
使用人工非病毒纳米治疗剂递送基因，包括质粒DNA、短干扰RNA（siRNA）和信使RNA（mRNA），是癌症基因治疗中有前途的方法。然而，全身给药后的多种生理屏障仍然是抗癌基因治疗剂临床转化的关键挑战。除了细胞外屏障，包括通过驻留的器官特异性巨噬细胞从血流中隔离基因递送纳米颗粒，以及它们在肿瘤中的不良外渗和组织渗透，克服细胞内屏障对于核酸的成功递送也是必要的。而对于RNA递送，内体屏障具有关键重要性，DNA货物的转移另外需要易位到细胞核中。更好地理解核酸纳米制剂跨越膜屏障对于改善当前非病毒载体至关重要。本文综述了非病毒纳米颗粒在细胞内转运的相关文献，并确定了克服细胞内屏障的关键因素。此外，最近的数据使我们能够对核酸纳米制剂的内体逃逸机制的当前假设提出新的解释。
Delivery of genes, including plasmid DNAs, short interfering RNAs (siRNAs), and messenger RNAs (mRNAs), using artificial non-viral nanotherapeutics is a promising approach in cancer gene therapy. However, multiple physiological barriers upon systemic administration remain a key challenge in clinical translation of anti-cancer gene therapeutics. Besides extracellular barriers including sequestration of gene delivery nanoparticles from the bloodstream by resident organ-specific macrophages, and their poor extravasation and tissue penetration in tumors, overcoming intracellular barriers is also necessary for successful delivery of nucleic acids. Whereas for RNA delivery the endosomal barrier holds a key importance, transfer of DNA cargo additionally requires translocation into the nucleus. Better understanding of crossing membrane barriers by nucleic acid nanoformulations is essential to the improvement of current non-viral carriers. This review aims to summarize relevant literature on intracellular trafficking of non-viral nanoparticles and determine key factors toward surmounting intracellular barriers. Moreover, recent data allowed us to propose new interpretations of current hypotheses of endosomal escape mechanisms of nucleic acid nanoformulations.
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影响因子：
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