Construction of an improved drug delivery system tool with enhanced versatility in cell-targeting.

Background/aim: The aim of this study was to develop an improved drug delivery system (DDS) tool with enhanced versatility in the cell-targeting step using as Z-domain, a modified IgG binding domain of protein A from Staphylococcus aureus, as an IgG adapter domain.

Materials And Methods: The chimera protein expression system composed of the Z-domain and chimeric cholesterol-dependent cytolysin mutant named His-Z-CDC(ss)(IS) was constructed in Escherichia coli. His-Z-CDC(ss)(IS) was purified by Ni-affinity chromatography, and its abilities for controlled pore formation, membrane binding, IgG binding, and target cell-specific delivery of liposomes carrying medicine were investigated.

Results And Discussion: His-Z-CDC(ss)(IS) purified by Ni-affinity chromatography indicated pore-forming activity only under disulfide bond reducing conditions. His-Z-CDC(ss)(IS) also demonstrated an ability to bind both IgG and cholesterol-embedded liposomes via its Z-domain and domain 4, respectively. Furthermore, anticarcinoembryonic antigen (CEA) IgG-bound His-Z-CDC(ss)(IS) indicated effective delivery of liposomes carrying drugs to CEA-expressing cells.

Conclusion: His-Z-CDC(ss)(IS) was revealed to be an improved DDS tool with enhanced versatility in cell targeting.