title: Thymidine kinase gene delivery using curcumin loaded peptide micelles as a combination therapy for glioblastoma.
abstract: OBJECTIVE
  The effect of the combination therapy of curcumin and the herpes simplex virus thymidine kinase (HSVtk) gene using R7L10 as a carrier was evaluated in a glioblastoma animal model.
  
  
  METHODS
  Curcumin was loaded into the cores of R7L10 peptide micelles using an oil-in-water emulsion/solvent evaporation method to generate curcumin loaded R7L10 micelles (R7L10-Cur), which were used as a carrier to deliver the HSVtk gene. The plasmid DNA (pDNA)/R7L10-Cur complex was confirmed by gel retardation, heparin competition, and dynamic light scattering analyses. Transfection efficiency and cytotoxicity were measured using luciferase, MTT, and TUNEL assays. Intracellular delivery of curcumin was determined by fluorescence and absorbance. In the glioblastoma animal model, the effects of the intratumoral delivery of curcumin and the HSVtk gene were evaluated according to tumor size, immunohistochemistry, and TUNEL assays.
  
  
  RESULTS
  R7L10-Cur delivered pDNA into the cells more efficiently than PLL and R7L10. In addition, R7L10-Cur delivered curcumin into the cells more efficiently than curcumin alone. The pHSVtk/R7L10-Cur complex induced cell death efficiently both in vitro and in vivo. Likewise, the combination of curcumin and the HSVtk gene using the pHSVtk/R7L10-Cur complex reduced tumor size more efficiently than the pHSVtk/PEI and pHSVtk/R7L10 complexes in a glioblastoma animal model.
  
  
  CONCLUSIONS
  R7L10 is an efficient carrier for delivery of curcumin and the HSVtk gene, which may be a useful combination therapy for glioblastoma.
authors.affiliation: BK21 Plus Future Biopharmaceutical Human Resources Training and Research Team, Department of Bioengineering, College of Engineering, Hanyang University, Seoul, 133-791, Republic of Korea.
authors.forename: Jin Hyeong
authors.initials: JH
authors.lastname: Park
authors.forename: Jaesik
authors.initials: J
authors.lastname: Han
authors.forename: Minhyung
authors.initials: M
authors.lastname: Lee
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003131:Combined Modality Therapy / Q000379:methods; D003474:Curcumin / Q000008:administration & dosage* / Q000378:metabolism; D018014:Gene Transfer Techniques; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D010455:Peptides / Q000008:administration & dosage* / Q000235:genetics; D051381:Rats; D013937:Thymidine Kinase / Q000008:administration & dosage* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D008823:Micelles; D010455:Peptides; D013937:Thymidine Kinase; D003474:Curcumin