Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan; Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
Adv Drug Deliv Rev. 2022 Sep;188:114417. doi: 10.1016/j.addr.2022.114417. Epub 2022 Jul 3.
A new era of nanomedicines that involve nucleic acids/gene therapy has been opened after two decades in 21st century and new types of more efficient drug delivery systems (DDS) are highly expected and will include extrahepatic delivery. In this review, we summarize the possibility and expectations for the extrahepatic delivery of small interfering RNA/messenger RNA/plasmid DNA/genome editing to the spleen, lung, tumor, lymph nodes as well as the liver based on our studies as well as reported information. Passive targeting and active targeting are discussed in in vivo delivery and the importance of controlled intracellular trafficking for successful therapeutic results are also discussed. In addition, mitochondrial delivery as a novel strategy for nucleic acids/gene therapy is introduced to expand the therapeutic dimension of nucleic acids/gene therapy in the liver as well as the heart, kidney and brain.
在 21 世纪的二十年之后，涉及核酸/基因治疗的纳米医学新时代已经开启，人们高度期待新型、更高效的药物输送系统（DDS），包括肝外输送。在这篇综述中，我们根据我们的研究和已报道的信息，总结了将小干扰 RNA/信使 RNA/质粒 DNA/基因组编辑递送到脾、肺、肿瘤、淋巴结以及肝脏的可能性和预期。讨论了在体内输送中被动靶向和主动靶向的作用，以及控制细胞内运输对于获得成功治疗效果的重要性。此外，还介绍了线粒体输送作为核酸/基因治疗的一种新策略，以扩展核酸/基因治疗在肝脏以及心脏、肾脏和大脑中的治疗维度。
