Bacterial cell killing by antibody targeted photolysis: enhanced effect by OH radical generation

Two structurally distinct immunoconjugates were used for photolysis of bacterial cells. One contained a dextran carbazate (DC) polymer as a linker between the photosensitizer molecules and the Fc oligosaccharide moiety of the monoclonal antibody, while the other linked the photosensitizer molecules and the Fc oligosaccharide by a short ethylenediamine (ED) spacer. The two immunoconjugates exhibited remarkably different photophysical properties and cell killing potential with respect to their abilities to generate singlet oxygen. The DC conjugate exhibited poor singlet oxygen (¹Δ_g) yields, yet was shown to produce more efficient cell killing on the basis of ¹Δ_g dose than did the ED conjugate. In light of the enhanced cell killing capacity of the DC conjugate, a search for other toxic photoproducts was initiated. It was found that the DC conjugate was capable of generating hydroxyl radicals (OH.) upon light illumination. Quantum yields for OH. generation were evaluated. The DC-photosensitizer polymer appeared to initiate a cascade addition reaction presumably by adding peroxides and hydroperoxides to the glucose residues of the dextran carbazate linker. These results suggest that this radical formation could propagate down the DC polymer and account for the superior cell killing exhibited by the DC conjugate.