title: Hepatitis B virus preS1-derived lipopeptide functionalized liposomes for targeting of hepatic cells.
abstract: To enhance the liver-specific delivery, HBVpreS/2-48(myr) (HBVP), a synthetic HBVpreS-derived lipopeptide endowed with compelling liver tropism, was conjugated to PEGylated liposomes (HBVP-Lip) for hepatic cell-specific delivery. Compared with the non-targeted liposomes, a significantly higher amount of HBVP-Lip were taken up by the primary mice hepatocytes through a receptor-mediated endocytosis mechanism. The endocytosis inhibition assay demonstrated that the endocytosis of HBVP-Lip was mediated mainly by caveolin and clathrin. After systemic administration in mice, HBVP-Lip could be specifically internalized into hepatocytes efficaciously. Furthermore, the hepatoprotective effects of HBVP-Lip loaded with silybin (SLB) on carbon tetrachloride induced acute liver damage were remarkably stronger than the SLB solution and SLB loaded non-targeted liposomes. Preliminary safety results suggested that no acute systemic toxicity or immunotoxicity was observed after intravenous administration with HBVP-Lip. These results indicated that the HBVP-Lip could deliver the payloads to the hepatocytes with high specificity in vitro and in vivo, and raise new possibilities for liver-specific drug delivery systems, gene delivery systems, and bio-imaging systems.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Xuanmiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Peng
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Longfei
authors.initials: L
authors.lastname: Liao
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Manchester M13 9PT, UK. Electronic address: ling.zhang@manchester.ac.uk.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. Electronic address: gongtaoy@126.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D006367:HeLa Cells; D006514:Hepatitis B Surface Antigens; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D058990:Molecular Targeted Therapy / Q000379:methods; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure*; D053761:Nanocomposites / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D011498:Protein Precursors / Q000493:pharmacokinetics*; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; D006514:Hepatitis B Surface Antigens; D008081:Liposomes; D053769:Nanocapsules; D011498:Protein Precursors; D012838:Silymarin; C050807:presurface protein 2, hepatitis B surface antigen; D000077385:Silybin
keywords: Hepatitis B virus; Hepatocytes; Liposomes; Liver; Targeted drug delivery