Convenient Preparation of Tumor-specific Immunoliposomes Containing Doxorubicin

Two innovative methods to prepare target-sensitive immunoliposomes containing doxorubicin by coupling monoclonal antibodies (mAb DH2, SH1) specific to cancer cell surface antigens ($G_{M3}$, $Le^X$) have been developed and are described here. Firstly, liposomes containing N-glutaryl phosphatidylethanolamine (NGPE) were prepared, followed by the encapsulation of doxorubicin, DH2 or SH1 antibodies were conjugated to NGPE in the liposomes (direct coupling). Secondly, liposomes were prepared with NGPE/mAb conjugates by the detergent dialysis method (conjugate insertion), and then doxorubicin was encapsulated by proton gradient. The immunoliposomes prepared by both methods were able to specifically bind to the surface of the tumor cells - B16BL6 mouse melanoma cells. The efficiencies of doxorubicin-entrapping into liposomes prepared by direct coupling and conjugate insertion was about 98% and 25%, respectively. These types of liposomal formulation are sensitive to target cells, which can be useful for various clinical applications.