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.
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