title: Improved therapeutic effect of DOX-PLGA-PEG micelles decorated with bivalent fragment HAb18 F(ab')(2) for hepatocellular carcinoma.
abstract: Although surgery offers the only hope of cure for hepatocellular carcinoma (HCC), patients with inoperable or metastatic disease have a dismal prognosis. Therefore, there is an urgent need for new and effective treatment strategies. Polymeric micelles composed of drug conjugated to a diblock copolymer have attracted great interest for clinical administration of anticancer drugs. In this work, characteristics and cytotoxicity of doxorubicin-poly(d,l-lactic-co-glycolic acid)-poly(ethylene glycol) (DOX-PLGA-PEG) micelle and its targeted micelle decorated with bivalent fragment HAb18 F(ab')(2) for HCC were studied. These micelles possessed spherical morphology and higher loading efficiency. Cellular uptake and accumulation in tumor tissue of micelles was observed. The accumulation of the targeted micelles depends on dual effects of passive and active targeting. The drug-loading micelles showed cytotoxicity on tumor cells in vitro and in vivo. The targeted micelles resulted in significant improvement in therapeutic response. These results suggest that the novel micelles could be a promising candidate with excellent therapeutic efficacy for targeting the drugs to cancer cells.
authors.affiliation: Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Jin
authors.forename: Niansong
authors.initials: N
authors.lastname: Qian
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Wenqing
authors.initials: W
authors.lastname: Yang
authors.forename: Ling
authors.initials: L
authors.lastname: Bai
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.forename: Minchang
authors.initials: M
authors.lastname: Wang
authors.forename: Wenjie
authors.initials: W
authors.lastname: Song
authors.forename: Kefeng
authors.initials: K
authors.lastname: Dou
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry / Q000627:therapeutic use*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D019344:Lactic Acid / Q000737:chemistry*; D008113:Liver Neoplasms / Q000188:drug therapy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D011092:Polyethylene Glycols / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments; D008823:Micelles; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D004317:Doxorubicin