School of Chemistry and Chemical Engineering, School of Biological and Pharmaceutical Engineering, Lanzhou Jiaotong University, Lanzhou 730070, Gansu, China; State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, Gansu, China.
State Key Laboratory of Veterinary Etiological Biology, Key Laboratory of Veterinary Parasitology of Gansu Province, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, Gansu, China.
Biomed Pharmacother. 2022 Jun;150:112945. doi: 10.1016/j.biopha.2022.112945. Epub 2022 Apr 8.
Alveolar echinococcosis caused by Echinococcus multilocularis is an important zoonotic disease, a great threat to human health due to limited interventions. microRNAs are a type of small non-coding RNA that plays a key role in many diseases and is considered as a potential therapeutic target for control of parasitic diseases. However, naked miRNAs are difficult to enter into cells and are easily degraded in both external and internal environments. Chitosan (CS) has recently been used as a promising vehicle for delivery of nucleic acids. Therefore, we prepared miRNA-bearing CS nanoparticles and investigated the physicochemical properties as well as the delivery efficiency. We found that CS nanoparticles was relatively stable, offered miRNA strong protection from degradation and had low cytotoxicity with no significant effects on cell proliferation and apoptosis. CS nanoparticles were shown to be easily absorbed by cells and have remarkable liver tropism. Furthermore, CS nanoparticles were used to efficiently deliver E. multilocularis miR-4989 in vitro and in vivo and caused a significant reduction in the expression of UBE2N in the liver, a potential target of emu-miR-4989, at both mRNA and protein levels. Our data demonstrate that CS nanoparticles can act as a vehicle for efficient liver-targeted delivery of miRNAs and for development of miRNA-based therapeutics against E. multilocularis infection.
泡型包虫病由多房棘球绦虫引起,是一种重要的人畜共患疾病,由于干预手段有限,对人类健康构成严重威胁。微小 RNA 是一种小型非编码 RNA,在许多疾病中发挥关键作用,被认为是控制寄生虫病的潜在治疗靶点。然而,裸露的微小 RNA 难以进入细胞,在内外环境中容易降解。壳聚糖 (CS) 最近已被用作递送核酸的有前途的载体。因此,我们制备了携带微小 RNA 的 CS 纳米颗粒,并研究了其理化性质和递送效率。我们发现 CS 纳米颗粒相对稳定,能为微小 RNA 提供强大的保护,防止其降解,且细胞毒性低,对细胞增殖和凋亡无显著影响。CS 纳米颗粒易于被细胞吸收,具有明显的肝脏趋向性。此外,CS 纳米颗粒在体外和体内有效递送至多房棘球绦虫 miR-4989,并导致肝脏中 UBE2N 的表达在 mRNA 和蛋白水平上均显著降低,UBE2N 是 emu-miR-4989 的一个潜在靶标。我们的数据表明,CS 纳米颗粒可作为一种载体,有效靶向递送至肝脏的微小 RNA,并为基于微小 RNA 的治疗多房棘球绦虫感染的方法提供了新的思路。