Trastuzumab-conjugated boron-containing liposomes for tumor-cell targeting; development and cellular studies.

The goal of the present study was to investigate HER-2-targeted boron-containing liposomes as a potential drug delivery vehicle for boron neutron capture therapy (BNCT). Trastuzumab was conjugated to the distal end of PEG-DSPE-NHS in micelles and the Trastuzumab-PEG-DSPE were then transferred to preformed liposomes, either empty or loaded with water soluble boronated acridine (WSA), using the micelle transfer method. The final conjugates were referred to as Trastuzumab-liposome and Trastuzumab-liposome-WSA. The binding specificity, uptake, retention and internalization of Trastuzumab-liposome-WSA conjugates were studied in cultured SK-BR-3 cells, with regard to the targeting agent, carrier, and the load. The subcellular location of WSA was studied using confocal microscopy. The conjugates showed specific binding to the HER-2 receptors of SK-BR-3 cells. High cellular uptake and internalization of the conjugates was seen, reaching 132 ppm of boron in the targeted cells after 24 h. WSA was distributed mainly in the cytoplasm and was shown to have long cellular retention, with 90% and 67% of the boron remained in the cells after 24 h and 48 h, respectively. The conjugate Trastuzumab-liposome-WSA could be considered as a potent drug delivery system for BNCT.