Della Pelle Giulia, Kostevšek Nina
Department for Nanostructured Materials, Jožef Stefan Institute, Jamova Cesta 39, 1000 Ljubljana, Slovenia.
Jožef Stefan International Postgraduate School, Jamova Cesta 39, 1000 Ljubljana, Slovenia.
Int J Mol Sci. 2021 May 17;22(10):5264. doi: 10.3390/ijms22105264.
Gene therapy has the potential to become a staple of 21st-century medicine. However, to overcome the limitations of existing gene-delivery therapies, that is, poor stability and inefficient and delivery and accumulation of nucleic acids (NAs), safe drug-delivery systems (DDSs) allowing the prolonged circulation and expression of the administered genes in vivo are needed. In this review article, the development of DDSs over the past 70 years is briefly described. Since synthetic DDSs can be recognized and eliminated as foreign substances by the immune system, new approaches must be found. Using the body's own cells as DDSs is a unique and exciting strategy and can be used in a completely new way to overcome the critical limitations of existing drug-delivery approaches. Among the different circulatory cells, red blood cells (RBCs) are the most abundant and thus can be isolated in sufficiently large quantities to decrease the complexity and cost of the treatment compared to other cell-based carriers. Therefore, in the second part, this article describes 70 years of research on the development of RBCs as DDSs, covering the most important RBC properties and loading methods. In the third part, it focuses on RBCs as the NA delivery system with advantages and drawbacks discussed to decide whether they are suitable for NA delivery in vivo.
基因治疗有潜力成为21世纪医学的一项主要手段。然而，为了克服现有基因递送疗法的局限性，即稳定性差以及核酸（NA）递送和积累效率低下的问题，需要安全的药物递送系统（DDS），以实现体内给药基因的长期循环和表达。在这篇综述文章中，简要描述了过去70年DDS的发展历程。由于合成DDS可能会被免疫系统识别并作为外来物质清除，因此必须寻找新的方法。利用人体自身细胞作为DDS是一种独特且令人兴奋的策略，可以以全新的方式克服现有药物递送方法的关键局限性。在不同的循环细胞中，红细胞（RBC）数量最为丰富，因此与其他基于细胞的载体相比，可以大量分离，从而降低治疗的复杂性和成本。因此，在第二部分，本文描述了将红细胞作为DDS的70年研究历程，涵盖了最重要的红细胞特性和加载方法。在第三部分，重点讨论了红细胞作为NA递送系统的优缺点，以确定它们是否适合体内NA递送。
