Sterically stabilized anti-G(M3), anti-Le(x) immunoliposomes: Targeting toB16BL6, HRT-18 cancer cells

Various tumor-associated antigens have been identified as carbohydrates bou nd to lipids or to proteins expressed on tumor cell membranes. We prepared tumor-specific immunoliposomes by coupling anticarbohydrate antibodies, suc h as antiganglioside G(M3) antibody (DH2) or anti-Le(x) antibody (SH1): to polyethylene glycol (PEG)-coated liposomes. In vitro and in vivo targetabil ity of anti-G(M3) and anti-Le(x) immunoliposomes to B16BL6 mouse melanoma c ells and HRT-18 human colorectal adenocarcinoma cells were monitored with a fluorescence microscopy, and analyzed by biodistribution assay of the immu noliposome in mice bearing the tumor tissues. The antibody coupling to the PEG liposomes did not greatly diminish the circulation time of the liposome in the C57BL/6 mouse model. In vitro cytotoxicity of doxorubicin encapsula ted in liposomes was enhanced by antibody coupling, but still behind free d oxorubicin. However, in vivo antitumor therapeutic efficacy of doxorubicin encapsulated in the immunoliposomes was far greater than the free drug or i n conventional liposomes. Doxorubicin encapsulated in anti-G(M3) immunolipo somes was able to reduce in vivo tumor growth and metastasis of B16BL6 mous e melanoma cells more greatly than any other formulations of the drug. This study suggests that tumor-associated antigens can be good target molecules for tumor-specific delivery of liposomal drugs or other synthetic drug del ivery systems.