title: Low-dose chemotherapy of hepatocellular carcinoma through triggered-release from bilayer-decorated magnetoliposomes.
abstract: Low-dose (LD) chemotherapy is a promising treatment strategy that may be improved by controlled delivery. Polyethylene glycol-stabilized bilayer-decorated magnetoliposomes (dMLs) have been designed as a stimuli-responsive LD chemotherapy drug delivery system and tested in vitro using Huh-7 hepatocellular carcinoma cell line. The dMLs contained hydrophobic superparamagnetic iron oxide nanoparticles within the lipid bilayer and doxorubicin hydrochloride (DOX, 2 μM) within the aqueous core. Structural analysis by cryogenic transmission electron microscopy and dynamic light scattering showed that the assemblies were approximately 120 nm in diameter. Furthermore, the samples consisted of a mixture of dMLs and bare liposomes (no nanoparticles), which provided dual burst and spontaneous DOX release profiles, respectively. Cell viability results show that the cytotoxicity of DOX-loaded dMLs was similar to that of bare dMLs (∼10%), which indicates that spontaneous DOX leakage had little cytotoxic effect. However, when subjected to a physiologically acceptable radiofrequency (RF) electromagnetic field, cell viability was reduced up to 40% after 8h and significant cell death (>90%) was observed after 24h. The therapeutic mechanism was intracellular RF-triggered DOX release from the dMLs and not intracellular hyperthermia due to nanoparticle heating via magnetic losses.
authors.affiliation: Department of Chemical Engineering, University of Rhode Island, 16 Greenhouse Road, Kingston, RI 02881, United States.
authors.forename: Yanjing
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, 7 Greenhouse Road, Kingston, RI 02881, United States.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, 7 Greenhouse Road, Kingston, RI 02881, United States.
authors.forename: Da
authors.initials: D
authors.lastname: Xiao
authors.affiliation: Department of Chemical Engineering, University of Rhode Island, 16 Greenhouse Road, Kingston, RI 02881, United States.
authors.forename: Arijit
authors.initials: A
authors.lastname: Bose
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, 7 Greenhouse Road, Kingston, RI 02881, United States.
authors.forename: Ruitang
authors.initials: R
authors.lastname: Deng
authors.affiliation: Department of Chemical Engineering, University of Rhode Island, 16 Greenhouse Road, Kingston, RI 02881, United States. Electronic address: bothun@egr.uri.edu.
authors.forename: Geoffrey D
authors.initials: GD
authors.lastname: Bothun
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D060526:Magnetic Fields; D011092:Polyethylene Glycols / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D008051:Lipid Bilayers; D008081:Liposomes; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: Drug delivery; Hepatocellular carcinoma; Magnetic nanoparticle; Magnetoliposome; SPIO nanoparticle; Stimuli responsive