title: IL-6 Antibody and RGD Peptide Conjugated Poly(amidoamine) Dendrimer for Targeted Drug Delivery of HeLa Cells.
abstract: In this study, PAMAM dendrimer (G4.5) was conjugated with two targeting moieties, IL-6 antibody and RGD peptide (G4.5-IL6 and G4.5-RGD conjugates). Doxorubicin anticancer drug was physically loaded onto G4.5-IL6 and G4.5-RGD with the encapsulation efficiency of 51.3 and 30.1% respectively. The cellular internalization and uptake efficiency of G4.5-IL6/DOX and G4.5-RGD/DOX complexes was observed and compared by confocal microscopy and flow cytometry using HeLa cells, respectively. The lower IC50 value of G4.5-IL6/DOX in comparison to G4.5-RGD/DOX is indication that higher drug loading and faster drug release rate corresponded with greater cytotoxicity. The cytotoxic effect was further verified by increment in late apoptotic/necrotic cells due to delivery of drug through receptor-mediated endocytosis. On the basis of these results, G4.5-IL6 is a better suited carrier for targeted drug delivery of DOX to cervical cancer cells.
authors.affiliation: Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology , Taipei 106, Taiwan ROC.
authors.forename: Shewaye Lakew
authors.initials: SL
authors.lastname: Mekuria
authors.affiliation: Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology , Taipei 106, Taiwan ROC.
authors.forename: Tilahun Ayane
authors.initials: TA
authors.lastname: Debele
authors.affiliation: Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology , Taipei 106, Taiwan ROC.
authors.forename: Hsiao-Ying
authors.initials: HY
authors.lastname: Chou
authors.affiliation: Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology , Taipei 106, Taiwan ROC.
authors.forename: Hsieh-Chih
authors.initials: HC
authors.lastname: Tsai
mesh_terms: D000906:Antibodies / Q000737:chemistry* / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015850:Interleukin-6 / Q000276:immunology*; D007700:Kinetics; D018613:Microscopy, Confocal; D009842:Oligopeptides / Q000737:chemistry*; D011073:Polyamines / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000906:Antibodies; D050091:Dendrimers; D015850:Interleukin-6; D009842:Oligopeptides; C531249:Poly(amidoamine); D011073:Polyamines; C047981:arginyl-glycyl-aspartic acid; D004317:Doxorubicin