Dual-functional liposome for tumor targeting and overcoming multidrug resistance in hepatocellular carcinoma cells.

Abstract

The purpose of this study was to design and evaluate the dual-functional liposome (LPG) with synthetic polymeric nano-biomaterial (Gal-P123) that targets cancer cells and reverses multidrug resistance (MDR) in hepatocellular carcinoma (HCC) cells. The mitoxantrone (MX) loaded LPG (MX-LPG) was about 100 nm in diameter, spherically shaped, and had an encapsulation efficiency of 97.3%. The cytotoxicity and cellular uptake of MX-LPG were evaluated in HCC Huh-7 cells. BCRP-overexpressing MDCKII/BCRP cells were used to certify the inhibitory effect of LPG on drug efflux transporter. Compared with MX, MX-LPG had 2.3-fold higher cytotoxicity in Huh-7 cells and a 14.9-fold increase in cellular MX accumulation in MDCKII/BCRP cells. The pharmacokinetic study in rats showed that LPG significantly prolonged the circulation time and enhanced the bioavailability of MX. Moreover, MX-LPG increased antitumor activity and improved selectivity in BALB/c mice bearing orthotopic xenograft HCC tumors.

• Authors: Xinxin Zhang, Shiyan Guo, Rong Fan, Miaorong Yu, Feifei Li, Chunliu Zhu, Yong Gan
• Journal: Biomaterials (Biomaterials) Vol. 33 Issue 29 Pg. 7103-14 (Oct 2012) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 22796159 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Liposomes
• Polymers
• Mitoxantrone

Topics

• Animals
• Carcinoma, Hepatocellular (metabolism)
• Cell Line, Tumor
• Drug Resistance, Multiple
• Humans
• Liposomes (chemistry)
• Liver Neoplasms (metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Mitoxantrone (pharmacology)
• Neoplasm Transplantation
• Neoplasms (pathology)
• Polymers (chemistry)
• Rats
• Rats, Sprague-Dawley
• Tissue Distribution