ABSTRACT: Cholesterol-dependent cytolysins (CDCs) are pore-forming toxins from Gram-positive bacteria. The aim of this study was to investigate the potential of a CDC, intermedilysin, as a drug-delivery system (DDS) for clinical application.
Intermedilysin was modified by the addition of a disulfide bridge to regulate pore formation, by swapping domain 4 to provide cholesterol-binding capacity, and by the introduction of a targeting domain. The resultant chimera protein, His-LTBP-CDC(ss)(IP), was investigated for its use as a DDS tool in vitro.
His-LTBP-CDC(ss)(IP) exhibited a regulated pore-forming capacity under reducing conditions. This chimera protein was able to deliver a drug-carrier liposome specifically to the target cell, to be endocytosed into the cell with subsequent release of the components into the cytoplasm.
A chimera protein derived from the bacterial pore-forming toxin intermedilysin (His-LTBP-CDC(ss)(IP)) forms the basis for a novel DDS tool.
Anticancer research 06/2012; 32(6):2323-9. · 1.73 Impact Factor