title: A safe and efficient hepatocyte-selective carrier system based on myristoylated preS1/21-47 domain of hepatitis B virus.
abstract: A safe and efficient liver targeted PEGylated liposome (PEG-Lip) based on N-terminal myristoylated preS1/21-47 (preS1/21-47(myr)) of hepatitis B virus was successfully developed. The study aimed to elucidate the cellular uptake mechanism of preS1/21-47(myr) modified PEG-Lip (preS1/21-47(myr)-PEG-Lip) in hepatogenic cells and the distribution behavior of preS1/21-47(myr)-PEG-Lip in Vr:CD1 (ICR) mice. The cellular uptake results showed that preS1/21-47(myr)-PEG-Lip was effectively taken up by hepatogenic cells (including primary hepatocytes and liver tumor cells) through a receptor-mediated endocytosis pathway compared with non-hepatogenic cells. After systemic administration to H22 hepatoma-bearing mice, preS1/21-47(myr)-PEG-Lip showed significant liver-specific delivery and an increase in the distribution of preS1/21-47(myr)-PEG-Lip in hepatic tumor. Furthermore, the antitumor effect of preS1/21-47(myr)-PEG-Lip loaded with paclitaxel (PTX) was remarkably stronger than that of PTX injection and PTX loaded liposomes (including common liposomes and PEG-Lip). In safety evaluation, no acute systemic toxicity and immunotoxicity were observed after intravenous injection of preS1/21-47(myr)-PEG-Lip. No liver toxicity was observed despite the dramatic increase of preS1/21-47(myr)-PEG-Lip in liver. Taken together, preS1/21-47(myr)-PEG-Lip represents a promising carrier system for targeted liver disease therapy and imaging.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. gongtaoy@126.com.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xuanmiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Tijia
authors.initials: T
authors.lastname: Chen
authors.forename: Xinyi
authors.initials: X
authors.lastname: Wang
authors.forename: Yao
authors.initials: Y
authors.lastname: Fu
authors.forename: Yun
authors.initials: Y
authors.lastname: Jin
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016503:Drug Delivery Systems / Q000379:methods*; D006514:Hepatitis B Surface Antigens / Q000737:chemistry / Q000494:pharmacology; D006515:Hepatitis B virus; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D008081:Liposomes; D054878:Lipoylation; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D011498:Protein Precursors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D006514:Hepatitis B Surface Antigens; D008081:Liposomes; D011498:Protein Precursors; C050806:presurface protein 1, hepatitis B surface antigen