title: Glycopolymer micelles with reducible ionic cores for hepatocytes-targeting delivery of DOX.
abstract: A novel galactose-decorated cross-linked micelles (cl-micelles) with ionic cores using cystamine (Cys) as a biodegradable cross-linker was prepared by using block ionomer complexes of poly(ethylene glycol)-b-poly(2-acryloxyethyl-galactose)-b-poly(acrylic acid) (PEG-b-PAEG-b-PAA) and Ca(2+) (PEG-b-PAEG-b-PAA cl-micelles/Cys). Doxorubicin (DOX) was successfully incorporated into the ionic cores of such micelles via electrostatic interactions. Proton nuclear magnetic resonance spectrum and Fourier transform infrared spectrometer indicated galactose ligands were exposed at the micellar surface. The micelles were spherical in shape, with an average size of 100nm. The in vitro release studies confirmed that DOX-loaded PEG-b-PAEG-b-PAA cl-micelles/Cys accomplished rapid drug release under reducing condition. Remarkably, PEG-b-PAEG-b-PAA cl-micelles/Cys efficiently delivered and released DOX into the cell nucleus of HepG2 cells, and the intensity of fluorescence observed in HepG2 cells was stronger than that incubated with the micelles without galactose ligands. In contrast, little fluorescence was observed in NIH3T3 cells after incubation with PEG-b-PAEG-b-PAA cl-micelles/Cys. Interestingly, cytotoxicity assays showed that DOX-loaded PEG-b-PAEG-b-PAA cl-micelles/Cys retained higher cell inhibition efficiency in HepG2 cells as compared with NIH3T3 cells, and were more potent than the micelles without galactose ligands and the micelles with non degradable cross-links. These results indicate that PEG-b-PAEG-b-PAA cl-micelles/Cys have great potential in liver tumor-targeted chemotherapy.
authors.affiliation: Key Laboratory of Functional Polymer Materials Ministry of Education, Institute of Polymer Chemistry, Nankai University, 94# Weijin Road, Tianjin 300071, China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Wang
authors.forename: Xinge
authors.initials: X
authors.lastname: Zhang
authors.forename: Peien
authors.initials: P
authors.lastname: Yu
authors.forename: Chaoxing
authors.initials: C
authors.lastname: Li
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003432:Cross-Linking Reagents / Q000737:chemistry; D003538:Cystamine / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005690:Galactose / Q000737:chemistry; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D008823:Micelles; D041681:NIH 3T3 Cells; D010316:Particle Size; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity
chemical_list: D000180:Acrylic Resins; D000903:Antibiotics, Antineoplastic; D003432:Cross-Linking Reagents; D008823:Micelles; C006903:carbopol 940; D004317:Doxorubicin; D003538:Cystamine; D005690:Galactose