Cargando…

Galactosylated Liposomes for Targeted Co-Delivery of Doxorubicin/Vimentin siRNA to Hepatocellular Carcinoma

The combination of therapeutic nucleic acids and chemotherapeutic drugs has shown great promise for cancer therapy. In this study, asialoglycoprotein receptors (ASGPR) targeting-ligand-based liposomes were tested to determine whether they can co-deliver vimentin siRNA and doxorubicin to hepatocellul...

Descripción completa

Detalles Bibliográficos
Autores principales: Oh, Hea Ry, Jo, Hyun-Young, Park, James S., Kim, Dong-Eun, Cho, Je-Yoel, Kim, Pyung-Hwan, Kim, Keun-Sik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5224624/
https://www.ncbi.nlm.nih.gov/pubmed/28335269
http://dx.doi.org/10.3390/nano6080141
_version_ 1782493395440107520
author Oh, Hea Ry
Jo, Hyun-Young
Park, James S.
Kim, Dong-Eun
Cho, Je-Yoel
Kim, Pyung-Hwan
Kim, Keun-Sik
author_facet Oh, Hea Ry
Jo, Hyun-Young
Park, James S.
Kim, Dong-Eun
Cho, Je-Yoel
Kim, Pyung-Hwan
Kim, Keun-Sik
author_sort Oh, Hea Ry
collection PubMed
description The combination of therapeutic nucleic acids and chemotherapeutic drugs has shown great promise for cancer therapy. In this study, asialoglycoprotein receptors (ASGPR) targeting-ligand-based liposomes were tested to determine whether they can co-deliver vimentin siRNA and doxorubicin to hepatocellular carcinoma (HCC) selectively. To achieve this goal, we developed an ASGPR receptor targeted co-delivery system called gal-doxorubicin/vimentin siRNA liposome (Gal-DOX/siRNA-L). The Gal-DOX/siRNA-L was created via electrostatic interaction of galactose linked-cationic liposomal doxorubicin (Gal-DOX-L) on vimentin siRNA. Previous studies have shown that Gal-DOX/siRNA-L inhibited tumor growth by combined effect of DOX and vimentin siRNA than single delivery of either DOX or vimentin siRNA. These Gal-DOX/siRNA-Ls showed stronger affinity to human hepatocellular carcinoma cells (Huh7) than other cells (lung epithelial carcinoma, A549). These liposomes also have demonstrated that novel hepatic drug/gene delivery systems composed of cationic lipid (DMKE: O,O’-dimyristyl-N-lysyl glutamate), cholesterol, galactosylated ceramide, POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine), and PEG(2000)-DSPE (distearoyl phosphatidyl ethanolamine) at 2:1:1:1:0.2 (moral ratios) can be used as an effective drug/gene carrier specifically targeting the liver in vivo. These results suggest that Gal-DOX-siRNA-L could effectively target tumor cells, enhance transfection efficacy and subsequently achieve the co-delivery of DOX and siRNA, demonstrating great potential for synergistic anti-tumor therapy.
format Online
Article
Text
id pubmed-5224624
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-52246242017-03-21 Galactosylated Liposomes for Targeted Co-Delivery of Doxorubicin/Vimentin siRNA to Hepatocellular Carcinoma Oh, Hea Ry Jo, Hyun-Young Park, James S. Kim, Dong-Eun Cho, Je-Yoel Kim, Pyung-Hwan Kim, Keun-Sik Nanomaterials (Basel) Article The combination of therapeutic nucleic acids and chemotherapeutic drugs has shown great promise for cancer therapy. In this study, asialoglycoprotein receptors (ASGPR) targeting-ligand-based liposomes were tested to determine whether they can co-deliver vimentin siRNA and doxorubicin to hepatocellular carcinoma (HCC) selectively. To achieve this goal, we developed an ASGPR receptor targeted co-delivery system called gal-doxorubicin/vimentin siRNA liposome (Gal-DOX/siRNA-L). The Gal-DOX/siRNA-L was created via electrostatic interaction of galactose linked-cationic liposomal doxorubicin (Gal-DOX-L) on vimentin siRNA. Previous studies have shown that Gal-DOX/siRNA-L inhibited tumor growth by combined effect of DOX and vimentin siRNA than single delivery of either DOX or vimentin siRNA. These Gal-DOX/siRNA-Ls showed stronger affinity to human hepatocellular carcinoma cells (Huh7) than other cells (lung epithelial carcinoma, A549). These liposomes also have demonstrated that novel hepatic drug/gene delivery systems composed of cationic lipid (DMKE: O,O’-dimyristyl-N-lysyl glutamate), cholesterol, galactosylated ceramide, POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine), and PEG(2000)-DSPE (distearoyl phosphatidyl ethanolamine) at 2:1:1:1:0.2 (moral ratios) can be used as an effective drug/gene carrier specifically targeting the liver in vivo. These results suggest that Gal-DOX-siRNA-L could effectively target tumor cells, enhance transfection efficacy and subsequently achieve the co-delivery of DOX and siRNA, demonstrating great potential for synergistic anti-tumor therapy. MDPI 2016-07-30 /pmc/articles/PMC5224624/ /pubmed/28335269 http://dx.doi.org/10.3390/nano6080141 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Oh, Hea Ry
Jo, Hyun-Young
Park, James S.
Kim, Dong-Eun
Cho, Je-Yoel
Kim, Pyung-Hwan
Kim, Keun-Sik
Galactosylated Liposomes for Targeted Co-Delivery of Doxorubicin/Vimentin siRNA to Hepatocellular Carcinoma
title Galactosylated Liposomes for Targeted Co-Delivery of Doxorubicin/Vimentin siRNA to Hepatocellular Carcinoma
title_full Galactosylated Liposomes for Targeted Co-Delivery of Doxorubicin/Vimentin siRNA to Hepatocellular Carcinoma
title_fullStr Galactosylated Liposomes for Targeted Co-Delivery of Doxorubicin/Vimentin siRNA to Hepatocellular Carcinoma
title_full_unstemmed Galactosylated Liposomes for Targeted Co-Delivery of Doxorubicin/Vimentin siRNA to Hepatocellular Carcinoma
title_short Galactosylated Liposomes for Targeted Co-Delivery of Doxorubicin/Vimentin siRNA to Hepatocellular Carcinoma
title_sort galactosylated liposomes for targeted co-delivery of doxorubicin/vimentin sirna to hepatocellular carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5224624/
https://www.ncbi.nlm.nih.gov/pubmed/28335269
http://dx.doi.org/10.3390/nano6080141
work_keys_str_mv AT ohheary galactosylatedliposomesfortargetedcodeliveryofdoxorubicinvimentinsirnatohepatocellularcarcinoma
AT johyunyoung galactosylatedliposomesfortargetedcodeliveryofdoxorubicinvimentinsirnatohepatocellularcarcinoma
AT parkjamess galactosylatedliposomesfortargetedcodeliveryofdoxorubicinvimentinsirnatohepatocellularcarcinoma
AT kimdongeun galactosylatedliposomesfortargetedcodeliveryofdoxorubicinvimentinsirnatohepatocellularcarcinoma
AT chojeyoel galactosylatedliposomesfortargetedcodeliveryofdoxorubicinvimentinsirnatohepatocellularcarcinoma
AT kimpyunghwan galactosylatedliposomesfortargetedcodeliveryofdoxorubicinvimentinsirnatohepatocellularcarcinoma
AT kimkeunsik galactosylatedliposomesfortargetedcodeliveryofdoxorubicinvimentinsirnatohepatocellularcarcinoma