Dual-functional liposome for tumor targeting and overcoming multidrug resistance in hepatocellular carcinoma cells.
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.
Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Science, Shanghai, China.
Xinxin
X
Zhang
Shiyan
S
Guo
Rong
R
Fan
Miaorong
M
Yu
Feifei
F
Li
Chunliu
C
Zhu
Yong
Y
Gan
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008942:Mitoxantrone / Q000494:pharmacology; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000473:pathology*; D011108:Polymers / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D008081:Liposomes; D011108:Polymers; D008942:Mitoxantrone