title: pH-sensitive pullulan-based nanoparticle carrier of methotrexate and combretastatin A4 for the combination therapy against hepatocellular carcinoma.
abstract: This study designs a pH-sensitive nanoparticle carrier of methotrexate (MTX) and combretastatin A4 (CA4) based on pullulan for the combination therapy against hepatocellular carcinoma (HCC). Briefly, N-urocanyl pullulan (URPA) with the degree of substitution (DS) of 5.2% was synthesized and then conjugated with MTX to form MTX-URPA, in which MTX content was 17.8%. MTX-URPA nanoparticles prepared by the dialysis method had spherical shape and the mean size of 187.1 nm, and showed high affinity for HepG2 cells. CA4 was successfully loaded into MTX-URPA nanoparticles and exhibited pH-sensitive in vitro release property. After intravenous injection to PLC/PRF/5-bearing nude mice, CA4 loaded MTX-URPA (CA4/MTX-URPA) nanoparticles achieved the enhanced antitumor and anti-angiogenic effects, the prolonged circulation time in blood, and the increased distributions both in the liver and the tumor. In conclusion, this drug carrier system has significant liver-targeting property and exhibits advantages for the combination therapy against hepatocellular carcinoma.
authors.affiliation: Research Center of Basic Medical Science, School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics) & Cancer Institute and Hospital, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, China. wangyinsong@tijmu.edu.cn
authors.forename: Yinsong
authors.initials: Y
authors.lastname: Wang
authors.forename: Hongli
authors.initials: H
authors.lastname: Chen
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Rongshan
authors.initials: R
authors.lastname: Li
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Yang
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D003692:Delayed-Action Preparations / Q000737:chemistry; D005936:Glucans / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008727:Methotrexate / Q000008:administration & dosage* / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008958:Models, Molecular; D053758:Nanoparticles / Q000737:chemistry*; D013267:Stilbenes / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D005936:Glucans; D013267:Stilbenes; C009109:pullulan; C058728:fosbretabulin; D008727:Methotrexate