title: Cytotoxic Effects of PEGylated Anti-EGFR Immunoliposomes Combined with Doxorubicin and Rhenium-188 Against Cancer Cells.
abstract: OBJECTIVE
  We aimed to construct epidermal growth factor receptor (EGFR)-targeting cetuximab-immunoliposomes (IL-C225) for targeted delivery of doxorubicin and rhenium-188 (Re-188) to EGFR(+) cancer cells.
  
  
  METHODS
  Synthesized IL-C225 was analyzed by dynamic light scattering, transmission electron microscopy, and matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy. Cell binding and internalization were examined using doxorubicin-loaded IL-C225 (DXR-IL-C225) with confocal microscopy. IL-C225 combined with doxorubicin and Re-188 ((188)Re-DXR-IL-C225) was synthesized, and the cytotoxic effects of (188)Re-DXR-IL-C225 were analyzed in EGFR(+) cancer cells using cell viability assays.
  
  
  RESULTS
  IL-C225 bound to EGFR on A431 cancer cells and was rapidly internalized. Furthermore, IL-C225 localized within the tumor cells efficiently. (188)Re-DXR-IL-C225 exhibited outstanding cytotoxic effects against EGFR(+) cancer cells in vitro and showed superior cytotoxic effects compared to DXR-IL-C225 or (188)Re-IL-C225 alone.
  
  
  CONCLUSIONS
  The new formulation of (188)Re-DXR-IL-C225 may be a potential theranostic vehicle for delivery of drugs in the treatment of EGFR-overexpressing human cancer.
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan, R.O.C. Division of Isotope Application, Institute of Nuclear Energy Research, Taoyuan, Taiwan, R.O.C.
authors.forename: Wei-Chuan
authors.initials: WC
authors.lastname: Hsu
authors.affiliation: Division of Isotope Application, Institute of Nuclear Energy Research, Taoyuan, Taiwan, R.O.C.
authors.forename: Chu-Nian
authors.initials: CN
authors.lastname: Cheng
authors.affiliation: Division of Isotope Application, Institute of Nuclear Energy Research, Taoyuan, Taiwan, R.O.C. jjhwang@ym.edu.tw twlee@iner.gov.tw.
authors.forename: Te-Wei
authors.initials: TW
authors.lastname: Lee
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan, R.O.C. jjhwang@ym.edu.tw twlee@iner.gov.tw.
authors.forename: Jeng-Jong
authors.initials: JJ
authors.lastname: Hwang
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000494:pharmacology*; D004705:Endocytosis / Q000187:drug effects; D066246:ErbB Receptors / Q000276:immunology*; D006801:Humans; D008081:Liposomes / Q000276:immunology* / Q000648:ultrastructure; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012211:Rhenium / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D008081:Liposomes; D011092:Polyethylene Glycols; D012211:Rhenium; D004317:Doxorubicin; D066246:ErbB Receptors
keywords: 188Re-DXR-IL-C225; Immunoliposomes; cytotoxicity; theranostic vehicle