title: Hepatoma-targeting and pH-sensitive nanocarriers based on a novel D-galactopyranose copolymer for efficient drug delivery.
abstract: Smart nanoparticles based on the mechanisms of asialoglycoprotein (ASGP)-mediated endocytosis and pH-induced drug release were developed for the efficient treatment of hepatoma using a newly developed copolymer, methoxy-polyethylene glycols (PEG)-b-poly (d-galactopyranose) (MPEG-b-PMaIPG). The particles exhibited spherical shapes, uniform particle size distribution (100 ± 4.43 nm), negative zeta potential (-32.8 ± 0.23 mV), high drug loading (24.77 ± 2.68%) and encapsulation efficiency (66.12 ± 9.44%). The in vitro drug release was also investigated, resulting that the release of drug from particles depended on different pH value. In vitro cell cytotoxicity and hemolysis assays were conducted to confirm the safety of the MPEG-b-PMaIPG nanoparticles. Anticancer activity showed that DOX-loaded MPEG-b-PMaIPG nanoparticles exhibited a high antitumor activity toward HepG2 cells, which was similar to free DOX, while blank MPEG-b-PMaIPG nanoparticles were non-toxic up to a tested concentration of 1.0mg/mL. Confocal laser scanning microscopy (CLSM) and flow cytometry (FCM) were used to verify the targeting efficiency of d-galactopyranose-modified nanoparticles. The results clearly demonstrated that d-galactopyranose-modified nanoparticles were taken up quickly by the HepG2 cells, which suggests that MPEG-b-PMaIPG nanoparticles with good biocompatibility and non-toxic for normal cells may be used as an effective cancer-targeting drug delivery system for chemotherapy.
authors.affiliation: School of Pharmacy, Binzhou Medical University, Yantai, PR China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ding
authors.affiliation: School of Pharmacy, Binzhou Medical University, Yantai, PR China. Electronic address: hanjingtian002@163.com.
authors.forename: Jingtian
authors.initials: J
authors.lastname: Han
authors.affiliation: School of Pharmacy, Binzhou Medical University, Yantai, PR China.
authors.forename: Baocheng
authors.initials: B
authors.lastname: Tian
authors.affiliation: School of Pharmacy, Binzhou Medical University, Yantai, PR China; Argenta Limited, PO Box 75 340, Manurewa 2102, Auckland, New Zealand.
authors.forename: Jian
authors.initials: J
authors.lastname: Han
authors.affiliation: School of Pharmacy, Binzhou Medical University, Yantai, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Binzhou Medical University, Yantai, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Pathology, Binzhou Medical University Hospital, Binzhou, PR China.
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Han
authors.affiliation: School of Chemistry and Chemical Engineering, University of Jinan, PR China. Electronic address: chm_peims@ujn.edu.cn.
authors.forename: Meishan
authors.initials: M
authors.lastname: Pei
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D065546:Drug Liberation; D004705:Endocytosis / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D005434:Flow Cytometry; D006461:Hemolysis / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008113:Liver Neoplasms / Q000378:metabolism*; D051379:Mice; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011109:Polymethacrylic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011109:Polymethacrylic Acids; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: Drug delivery; Hepatoma-targeting; Nanoparticles; d-Galactopyranose; pH-sensitive