A boronate-based modular assembly nanosystem to block the undesirable crosstalk between hepatic stellate cells and Kupffer cells

Huizhen Jia, Ling Ding, Ao Yu, Weimin Tang, Siyuan Tang, Chuhan Zhang, David Oupický

Research output: Contribution to journalArticlepeer-review

Abstract

Crosstalk between Kupffer cells (KCs) and hepatic stellate cells (HSCs) plays an important role in multiple liver disease conditions, including the formation of liver fibrosis in alcohol-associated liver disease (AALD). Therapeutic targeting of the KC-HSC crosstalk is a prime target for therapeutic interventions. Herein, a novel modular nanosystem was designed and prepared through the self-assembly utilizing boric acid and catechol interactions to prepare polymers modified with a CXCR4-inhibiting moieties. The polymers were used to encapsulate anti-miR-155 and to block the undesirable crosstalk between HSCs and KCs by downregulating miR-155 expression in KCs with the parallel inhibition of CXCR4 signaling in activated HSCs. The combined inhibition of miR-155 and CXCR4 at two different liver cell types achieved improved antifibrosis effects in a mouse model of AALD fibrosis. Our finding highlights the key role that blocking the undesirable crosstalk between HSCs and KCs plays in reversing AALD fibrosis as well as demonstrates a proof-of-concept approach for designing and constructing multifunctional delivery nanosystems using orthogonal functional modules based on the understanding of disease mechanisms.

Original languageEnglish (US)
JournalBioactive Materials
DOIs
StateAccepted/In press - 2022

Keywords

  • CXCR4
  • Liver fibrosis
  • miRNA
  • Modular assembly
  • Nanoparticles
  • Undesirable crosstalk

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biomedical Engineering

Fingerprint

Dive into the research topics of 'A boronate-based modular assembly nanosystem to block the undesirable crosstalk between hepatic stellate cells and Kupffer cells'. Together they form a unique fingerprint.

Cite this