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Efficient delivery of Echinococcus multilocularis miRNAs using chitosan nanoparticles - 27/05/22

Doi : 10.1016/j.biopha.2022.112945 
Yue Sun a, b, 1, Yongjie Kou b, 1, Xuedong He b, Yuting Yan b, Xiaola Guo b, Xing Yang c, Naipu He a, William C. Cho d, Ivan Kutyrev e, f, Majid Fasihi Harandi g, Omnia M. Kandil h, Xiaoqiang Wang a, , Houhui Song i, , Yadong Zheng i,
a School of Chemistry and Chemical Engineering, School of Biological and Pharmaceutical Engineering, Lanzhou Jiaotong University, Lanzhou 730070, Gansu, China 
b 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 
c Department of Medical Microbiology and Immunology, School of Basic Medicine, Dali University, Dali 671000, Yunnan, China 
d Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong SAR, China 
e Institute of General and Experimental Biology, Siberian Branch of Russian Academy of Sciences, Sakhyanovoi st. 6, 670047 Ulan-Ude, Russia 
f Institute of Biology, Irkutsk State University, Irkutsk 664025, Russia 
g Research Center for Hydatid Disease in Iran, Kerman University of Medical Sciences, Kerman 7616914115, Iran 
h Depterment of Parasitology and Animal Disease, Veterinary Research Institute, National Research Centre, Giza 12622, Egypt 
i Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Zhejiang Provincial Engineering Laboratory for Animal Health Inspection & Internet Technology, Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management, China-Australia Joint Laboratory for Animal Health Big Data Analytics, College of Animal Science and Technology & College of Veterinary Medicine of Zhejiang A&F University, Hangzhou 311300, China 

Correspondence to: 666 Wusu Street, Lin’an District, Hangzhou 311300, Zhejiang, China.666 Wusu Street, Lin’an DistrictHangzhouZhejiang311300China

Abstract

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.

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Highlights

CS nanoparticles was relatively stable and lowly cytotoxic and offered miRNA strong protection.
CS nanoparticles were easily absorbed by cells and showed remarkable liver tropism.
CS nanoparticles were efficient to deliver E. multilocularis miR-4989 in vitro and in vivo.
CS nanoparticles are a promising vehicle for development of miRNA-bases therapeutics against AE.

El texto completo de este artículo está disponible en PDF.

Keywords : Echinococcus multilocularis, Chitosan, MiRNA, CS nanoparticle, Emu-miR-4989


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© 2022  The Authors. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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