TY - JOUR
T1 - Engineered Relaxin as theranostic nanomedicine to diagnose and ameliorate liver cirrhosis
AU - Nagórniewicz, Beata
AU - Mardhian, Deby F.
AU - Booijink, Richell
AU - Storm, Gert
AU - Prakash, Jai
AU - Bansal, Ruchi
N1 - Elsevier deal
PY - 2019/4/1
Y1 - 2019/4/1
N2 -
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.
AB -
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.
KW - UT-Hybrid-D
KW - Hepatic stellate cells
KW - Nanomedicine
KW - Relaxin
KW - Superparamagnetic iron-oxide nanoparticles (SPIONs)
KW - Theranostics
KW - Cirrhosis
UR - http://www.scopus.com/inward/record.url?scp=85061379976&partnerID=8YFLogxK
U2 - 10.1016/j.nano.2018.12.008
DO - 10.1016/j.nano.2018.12.008
M3 - Article
AN - SCOPUS:85061379976
SN - 1549-9634
VL - 17
SP - 106
EP - 118
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
ER -