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)

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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

Fingerprint

Relaxin
Medical nanotechnology
Liver Cirrhosis
Liver
Hepatic Stellate Cells
Pharmacokinetics
Medical problems
Iron oxides
Therapeutics
Nanoparticles
Imaging techniques
Cell Movement
Theranostic Nanomedicine
Early Diagnosis
Cell Differentiation
Fibrosis
Mortality
Health

Keywords

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

Cite this

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title = "Engineered Relaxin as theranostic nanomedicine to diagnose and ameliorate liver cirrhosis",
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.",
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Engineered Relaxin as theranostic nanomedicine to diagnose and ameliorate liver cirrhosis. / Nagórniewicz, Beata; Mardhian, Deby F.; Booijink, Richell; Storm, Gert; Prakash, Jai; Bansal, Ruchi (Corresponding Author).

In: Nanomedicine: Nanotechnology, Biology, and Medicine, Vol. 17, 01.04.2019, p. 106-118.

Research output: Contribution to journalArticleAcademicpeer-review

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