Engineered Relaxin as theranostic nanomedicine to diagnose and ameliorate liver cirrhosis

Beata Nagórniewicz, Deby F. Mardhian, Richell Booijink, Gert Storm, Jai Prakash, Ruchi Bansal* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Hepatic cirrhosis is a growing health problem with increasing mortality worldwide. So far, there is a lack of early diagnosis and no clinical therapy is approved for the treatment. In this study, we developed a novel theranostic nanomedicine by targeting relaxin (RLX) that is known to possess potent anti-fibrotic properties but simultaneously has poor pharmacokinetics and detrimental off-target effects. We conjugated RLX to PEGylated superparamagnetic iron-oxide nanoparticles (RLX-SPIONs) and examined hepatic stellate cells (HSCs) specific binding/uptake. Thereafter, we assessed the therapeutic efficacy of RLX-SPIONs on human HSCs in vitro and in vivo in CCl 4 -induced liver cirrhosis mouse model. RLX-SPIONs showed specific binding and uptake in TGFβ-activated HSCs, and inhibited TGFβ-induced HSCs differentiation, migration and contraction. In vivo, RLX-SPIONs strongly attenuated cirrhosis and showed enhanced contrast in MR imaging. Altogether, this study presents RLX-SPIONs as a novel theranostic nanomedicine that provides new opportunities for the diagnosis and treatment of liver cirrhosis.

Original languageEnglish
Pages (from-to)106-118
Number of pages13
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume17
DOIs
Publication statusPublished - 1 Apr 2019

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Keywords

  • UT-Hybrid-D
  • Hepatic stellate cells
  • Nanomedicine
  • Relaxin
  • Superparamagnetic iron-oxide nanoparticles (SPIONs)
  • Theranostics
  • Cirrhosis

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