Ginger exosome-like nanoparticle-derived miRNA therapeutics: A strategic inhibitor of intestinal inflammation

Ling Yan; Yaqi Cao; Linhai Hou; Tianyu Luo; Meiqi Li; Shengjie Gao; Lei Wang; Kangliang Sheng; Lei Zheng

doi:10.1016/j.jare.2024.04.001

Ginger exosome-like nanoparticle-derived miRNA therapeutics: A strategic inhibitor of intestinal inflammation

J Adv Res. 2024 Apr 6:S2090-1232(24)00130-9. doi: 10.1016/j.jare.2024.04.001. Online ahead of print.

Authors

Ling Yan¹, Yaqi Cao², Linhai Hou², Tianyu Luo², Meiqi Li², Shengjie Gao², Lei Wang², Kangliang Sheng³, Lei Zheng⁴

Affiliations

¹ School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China; Engineering Research Center of Bio-Process, Ministry of Education, School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China.
² School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China.
³ School of Life Sciences, Anhui University, Hefei, Anhui 230601, China. Electronic address: kangliang@ahu.edu.cn.
⁴ School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China; Engineering Research Center of Bio-Process, Ministry of Education, School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China. Electronic address: lei.zheng@aliyun.com.

PMID: 38588850
DOI: 10.1016/j.jare.2024.04.001

Abstract

Introduction: MicroRNAs (miRNAs) involve in destabilising messenger RNA or repressing translation of target molecules. Ginger-derived exosome-like nanoparticles (GELNs) play a crucial role in modulating intestinal inflammation. Moreover, GELNs contain highly heterogeneous miRNA. However, the role of miRNAs derived from GELNs in immunomodulation remains unclear.

Objectives: This study aimed to elucidate the molecular basis of the unique biological effects mediated by miRNA derived from GELNs on macrophages.

Methods: GELNs were isolated using a combination of commercial exosome isolation kits and the differential centrifugation method, and the lipid composition of GELNs was determined using liquid chromatography-mass spectrometry. Subsequently, PKH26 labelled GELNs were taken up by macrophages. Furthermore, the modulation of inflammatory and immune responses by GELNs or osa-miR164d was assessed through the RNA-seq, RT-qPCR, online databases, and dual luciferase reporter assays to explore the underlying mechanisms of osa-miR164d. Biomimetic exosomes loaded with osa-miR164d were prepared using a microfluidic mixing device and systematically characterized. The therapeutic effects of osa-miR164d on relieving colitis were evaluated.

Results: We report for the first time that GELNs-derived osa-miR164d is a regulatory factor of reprogramming macrophage polarization, thereby inhibiting the intestinal inflammatory response. Mechanistically, osa-miR164d directly targets the 3'-UTRs of TAB1, which regulates macrophage polarization through the downregulation of NF-κB expression. In addition, We have designed a biomimetic exosome mimicking GELNs to deliver osa-miR164d (osa-miR164d-MGELNs). Notably, the osa-miR164d-MGELNs can efficiently reprogram macrophages to alleviate colitis-related symptoms.

Conclusion: Our findings enhance the systematic understanding of how GELNs-derived osa-miR164d mediates cross-kingdom communication and provide an original engineering paradigm for mimicking GELNs to transfer miRNA.

Keywords: Cross-kingdom communication; Exosome-like nanoparticles; Ginger; Inflammatory responses; miRNAs.