title: Pre-targeting and direct immunotargeting of liposomal drug carriers to ovarian carcinoma.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) is overexpressed in many solid tumor types, such as ovarian carcinoma. Immunoliposome based drug targeting has shown promising results in drug delivery to the tumors. However, the ratio of tumor-to-normal tissue concentrations should be increased to minimize the adverse effects of cytostatic drugs.
  
  
  RESULTS
  We studied the EGFR-targeted doxorubicin immunoliposomes using pre-targeting and local intraperitoneal (i.p.) administration of the liposomes. This approach was used to increase drug delivery to tumors as compared to direct intravenous (i.v.) administration of liposomes. EGFR antibodies were attached on the surface of PEG coated liposomes using biotin-neutravidin binding. Receptor mediated cellular uptake and cytotoxic efficacy of EGFR-targeted liposomes were investigated in human ovarian adenocarcinoma (SKOV-3 and SKOV3.ip1) cells. In vivo distribution of the liposomes in mice was explored using direct and pre-targeting approaches and SPECT/CT imaging. Targeted liposomes showed efficient and specific receptor-mediated binding to ovarian carcinoma cells in vitro, but the difference in cytotoxicity between targeted and non-targeted liposomes remained small. The relatively low cytotoxic efficacy is probably due to insufficient doxorubicin release from the liposomes rather than lack of target binding. Tumor uptake of targeted liposomes in vivo was comparable to that of non-targeted liposomes after both direct and pre-targeting administration. For both EGFR-targeted and non-targeted liposomes, the i.p. administration increased liposome accumulation to the tumors compared to i.v. injections.
  
  
  CONCLUSIONS
  Intraperitoneal administration of liposomes may be a beneficial approach to treat the tumors in the abdominal cavity. The i.p. pre-targeting method warrants further studies as a potential approach in cancer therapy.
authors: Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland. julia.lehtinen@helsinki.fi
authors: Julia
authors: J
authors: Lehtinen
authors: Mari
authors: M
authors: Raki
authors: Kim A
authors: KA
authors: Bergström
authors: Päivi
authors: P
authors: Uutela
authors: Katariina
authors: K
authors: Lehtinen
authors: Annukka
authors: A
authors: Hiltunen
authors: Jere
authors: J
authors: Pikkarainen
authors: Huamin
authors: H
authors: Liang
authors: Sari
authors: S
authors: Pitkänen
authors: Ann-Marie
authors: AM
authors: Määttä
authors: Raimo A
authors: RA
authors: Ketola
authors: Marjo
authors: M
authors: Yliperttula
authors: Thomas
authors: T
authors: Wirth
authors: Arto
authors: A
authors: Urtti
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism; D061067:Antibodies, Monoclonal, Humanized; D001360:Avidin / Q000378:metabolism; D001710:Biotin / Q000378:metabolism; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D000068818:Cetuximab; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D066246:ErbB Receptors / Q000276:immunology / Q000378:metabolism; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008081:Liposomes; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods*; D064847:Multimodal Imaging; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D049268:Positron-Emission Tomography; D014057:Tomography, X-Ray Computed
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D008081:Liposomes; C093483:neutravidin; D001360:Avidin; D001710:Biotin; D004317:Doxorubicin; D066246:ErbB Receptors; D000068818:Cetuximab