Targeting Stealth liposomes in a murine model of human small cell lung cancer.
Tumor accumulation and therapeutic activity of Stealth liposomes loaded with doxorubicin (DXR) were examined in Balb/c nude mice xenografts inoculated subcutaneously with the human small cell lung cancer (SCLC) cell line, H69. Mice were treated with non-targeted liposomes (SL) or liposomes targeted with antagonist G coupled to the liposome surface (SLG). SLG showed 30-44-fold higher binding to H69 cells harvested from H69 xenografts than SL. At 48 and 72 h post injection, tumor accumulation of [(125)I]tyraminylinulin-containing liposomes was shown to be dependent on liposome size but independent of the presence of the targeting ligand. Maximum tumor uptake of either SLG or SL ranged from 2 to 4% of injected dose/g of tissue. In therapeutic studies, mice received three weekly injections of 3 or 6 mg free DXR/kg or 3 or 10 mg liposomal DXR/kg at initial tumor volumes of either 7 or 33 mm(3). The therapeutic efficacy of DXR-containing SL or SLG was significantly improved over free DXR, but SLG did not improve anti-tumor efficacy relative to SL. Stealth liposomes containing DXR have potential as a therapy against human SCLC tumors.
Moreira
J N
JN
Department of Pharmacology, University of Alberta, Edmonton, Canada.
Gaspar
R
R
Allen
T M
TM
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008081:Liposomes; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D008081:Liposomes; D004317:Doxorubicin