Targeting Stealth liposomes in a murine model of human small cell lung cancer

Tumor accumulation and therapeutic activity of Stealth liposomes loaded wit h 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-f old higher binding to H69 cells harvested from H69 xenografts than SL. At 4 8 and 72 h post injection, tumor accumulation of [I-125]tyraminylinulin-con taining liposomes was shown to be dependent on liposome size but independen t of the presence of the targeting ligand. Maximum tumor uptake of either S LG or SL ranged from 2 to 4% of injected dose/g of tissue. In therapeutic s tudies, 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 im proved 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. (C) 2001 Elsevier Science B,V. All rights reserved.