Cargando…

Protective effect of Gelofusine against cRGD-siRNA-induced nephrotoxicity in mice

Based on successful targeting to the αvβ3 integrin of cyclic arginine–glycine–aspartic acid (cRGD), cRGD-conjugated small interfering RNA (siRNA) exhibits tumor targeting and has become a new treatment strategy for solid tumors. However, the nephrotoxicity caused by its renal retention limits its cl...

Descripción completa

Detalles Bibliográficos
Autores principales: Liao, Wenjie, Qin, Yixin, Liao, Lumin, Cen, Bohong, Wu, Zhuomin, Wei, Yuanyi, Wang, Zhen, Li, Guoxian, Ji, Aimin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6014494/
https://www.ncbi.nlm.nih.gov/pubmed/29619875
http://dx.doi.org/10.1080/0886022X.2018.1450761
_version_ 1783334245947670528
author Liao, Wenjie
Qin, Yixin
Liao, Lumin
Cen, Bohong
Wu, Zhuomin
Wei, Yuanyi
Wang, Zhen
Li, Guoxian
Ji, Aimin
author_facet Liao, Wenjie
Qin, Yixin
Liao, Lumin
Cen, Bohong
Wu, Zhuomin
Wei, Yuanyi
Wang, Zhen
Li, Guoxian
Ji, Aimin
author_sort Liao, Wenjie
collection PubMed
description Based on successful targeting to the αvβ3 integrin of cyclic arginine–glycine–aspartic acid (cRGD), cRGD-conjugated small interfering RNA (siRNA) exhibits tumor targeting and has become a new treatment strategy for solid tumors. However, the nephrotoxicity caused by its renal retention limits its clinical application. Here, we evaluated the protective effect of Gelofusine against cRGD-conjugated siRNA-induced nephrotoxicity in mice. Male Kunming mice (six per group) were either co-injected with Gelofusine and cRGD-siRNA or injected with cRGD-siRNA alone. After administration of these treatments five times, creatinine and blood urea nitrogen (BUN) levels were determined. Hematoxylin–eosin staining (HE staining) and transferase dUTP nick end labeling (TUNEL) analysis were used to compare the difference in renal damage between the groups. Additionally, fluorescence imaging was used to observe the distribution of cRGD-siRNA in vivo. The group co-injected with Gelofusine and cRGD-siRNA displayed lower creatinine and BUN levels than the cRGD-siRNA-alone group and showed less renal damage upon HE staining and TUNEL analysis. Gelofusine decreased the retention time and accelerated the elimination of cRGD-siRNA from the organs, as observed in the fluorescence images. These data indicate that Gelofusine significantly increased the excretion of cRGD-conjugated siRNA and reduced the associated renal damage.
format Online
Article
Text
id pubmed-6014494
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Taylor & Francis
record_format MEDLINE/PubMed
spelling pubmed-60144942018-06-28 Protective effect of Gelofusine against cRGD-siRNA-induced nephrotoxicity in mice Liao, Wenjie Qin, Yixin Liao, Lumin Cen, Bohong Wu, Zhuomin Wei, Yuanyi Wang, Zhen Li, Guoxian Ji, Aimin Ren Fail Laboratory Study Based on successful targeting to the αvβ3 integrin of cyclic arginine–glycine–aspartic acid (cRGD), cRGD-conjugated small interfering RNA (siRNA) exhibits tumor targeting and has become a new treatment strategy for solid tumors. However, the nephrotoxicity caused by its renal retention limits its clinical application. Here, we evaluated the protective effect of Gelofusine against cRGD-conjugated siRNA-induced nephrotoxicity in mice. Male Kunming mice (six per group) were either co-injected with Gelofusine and cRGD-siRNA or injected with cRGD-siRNA alone. After administration of these treatments five times, creatinine and blood urea nitrogen (BUN) levels were determined. Hematoxylin–eosin staining (HE staining) and transferase dUTP nick end labeling (TUNEL) analysis were used to compare the difference in renal damage between the groups. Additionally, fluorescence imaging was used to observe the distribution of cRGD-siRNA in vivo. The group co-injected with Gelofusine and cRGD-siRNA displayed lower creatinine and BUN levels than the cRGD-siRNA-alone group and showed less renal damage upon HE staining and TUNEL analysis. Gelofusine decreased the retention time and accelerated the elimination of cRGD-siRNA from the organs, as observed in the fluorescence images. These data indicate that Gelofusine significantly increased the excretion of cRGD-conjugated siRNA and reduced the associated renal damage. Taylor & Francis 2018-04-05 /pmc/articles/PMC6014494/ /pubmed/29619875 http://dx.doi.org/10.1080/0886022X.2018.1450761 Text en © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Laboratory Study
Liao, Wenjie
Qin, Yixin
Liao, Lumin
Cen, Bohong
Wu, Zhuomin
Wei, Yuanyi
Wang, Zhen
Li, Guoxian
Ji, Aimin
Protective effect of Gelofusine against cRGD-siRNA-induced nephrotoxicity in mice
title Protective effect of Gelofusine against cRGD-siRNA-induced nephrotoxicity in mice
title_full Protective effect of Gelofusine against cRGD-siRNA-induced nephrotoxicity in mice
title_fullStr Protective effect of Gelofusine against cRGD-siRNA-induced nephrotoxicity in mice
title_full_unstemmed Protective effect of Gelofusine against cRGD-siRNA-induced nephrotoxicity in mice
title_short Protective effect of Gelofusine against cRGD-siRNA-induced nephrotoxicity in mice
title_sort protective effect of gelofusine against crgd-sirna-induced nephrotoxicity in mice
topic Laboratory Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6014494/
https://www.ncbi.nlm.nih.gov/pubmed/29619875
http://dx.doi.org/10.1080/0886022X.2018.1450761
work_keys_str_mv AT liaowenjie protectiveeffectofgelofusineagainstcrgdsirnainducednephrotoxicityinmice
AT qinyixin protectiveeffectofgelofusineagainstcrgdsirnainducednephrotoxicityinmice
AT liaolumin protectiveeffectofgelofusineagainstcrgdsirnainducednephrotoxicityinmice
AT cenbohong protectiveeffectofgelofusineagainstcrgdsirnainducednephrotoxicityinmice
AT wuzhuomin protectiveeffectofgelofusineagainstcrgdsirnainducednephrotoxicityinmice
AT weiyuanyi protectiveeffectofgelofusineagainstcrgdsirnainducednephrotoxicityinmice
AT wangzhen protectiveeffectofgelofusineagainstcrgdsirnainducednephrotoxicityinmice
AT liguoxian protectiveeffectofgelofusineagainstcrgdsirnainducednephrotoxicityinmice
AT jiaimin protectiveeffectofgelofusineagainstcrgdsirnainducednephrotoxicityinmice