Shu Zhaoma, Ota Azumi, Takayama Yukiya, Katsurada Yuri, Kusamori Kosuke, Abe Naoko, Nakamoto Kosuke, Tomoike Fumiaki, Tada Seiichi, Ito Yoshihiro, Nishikawa Makiya, Kimura Yasuaki, Abe Hiroshi
Department of Chemistry, Nagoya University.
Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science.
Chem Pharm Bull (Tokyo). 2020;68(2):129-132. doi: 10.1248/cpb.c19-00811.
Efficient methods for delivery of antisense DNA or small interfering RNA (siRNA) are highly needed. Cationic materials, which are conventionally used for anionic oligonucleotide delivery, have several drawbacks, including aggregate formation, cytotoxicity and a low endosome escape efficiency. In this report a bio-reactive mask (i.e., disulfide unit) for cationic amino groups was introduced, and the mask was designed such that it was removed at the target cell surface. Insolubility and severe cellular toxicity caused by exposed cationic groups are avoided when using the mask. Moreover, the disulfide unit used to mask the cationic group enabled direct delivery of oligonucleotides to the cell cytosol. The molecular design reported is a promising approach for therapeutic applications.
迫切需要高效的反义DNA或小干扰RNA（siRNA）递送方法。传统上用于阴离子寡核苷酸递送的阳离子材料存在几个缺点，包括聚集体形成、细胞毒性和低内体逃逸效率。在本报告中，引入了一种用于阳离子氨基的生物反应性掩蔽基团（即二硫键单元），并且该掩蔽基团的设计使其在靶细胞表面被去除。使用该掩蔽基团可避免因暴露的阳离子基团导致的不溶性和严重细胞毒性。此外，用于掩蔽阳离子基团的二硫键单元能够将寡核苷酸直接递送至细胞胞质溶胶。所报道的分子设计是一种有前景的治疗应用方法。
