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 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 PEG2000-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.
Department of Biomedical Laboratory Science, Konyang University, Daejeon 35365, Korea. hearyoh10@gmail.com.
Hea Ry
HR
Oh
Department of Biomedical Laboratory Science, Konyang University, Daejeon 35365, Korea. hyun02for@hanmail.net.
Hyun-Young
HY
Jo
Department of Medicine, New York University School of Medicine, New York, NY 10016, USA. james.park@nyumc.org.
James S
JS
Park
Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea. kimde@konkuk.ac.kr.
Dong-Eun
DE
Kim
Department of Biochemistry, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea. jeycho@snu.ac.kr.
Je-Yoel
JY
Cho
Department of Biomedical Laboratory Science, Konyang University, Daejeon 35365, Korea. kimph1010@konyang.ac.kr.
Pyung-Hwan
PH
Kim
Department of Biomedical Laboratory Science, Konyang University, Daejeon 35365, Korea. kskim11@konyang.ac.kr.
Keun-Sik
KS
Kim
co-delivery; combination therapy; doxorubicin; hepatocellular carcinoma; targeted liposomes; vimentin siRNA