Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 17, Issue -, Pages 106-118Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2018.12.008
Keywords
Relaxin; Superparamagnetic iron-oxide nanoparticles (SPIONs); Hepatic stellate cells; Cirrhosis; Theranostics; Nanomedicine
Funding
- Netherlands Organization for Health Research and Development (ZonMW, NWO) [916.151.94]
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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 CCl4-induced liver cirrhosis mouse model. RLX-SPIONs showed specific binding and uptake in TGF beta-activated HSCs, and inhibited TGF beta-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. (C) 2019 The Authors. Published by Elsevier Inc.
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