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 oligosaccharid e moiety of the monoclonal antibody, while the other linked the photos ensitizer molecules and the Fc oligosaccharide by a short ethylenediam ine (ED) spacer. The two immunoconjugates exhibited remarkably differe nt photophysical properties and cell killing potential with respect to their abilities to generate singlet oxygen. The DC conjugate exhibite d poor singlet oxygen ((1) Delta(g)) yields, yet was shown to produce more efficient cell killing on the basis of (1) Delta(g), dose than di d 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 hydroxy l radicals (OH.) upon light illumination. Quantum yields for OH. gener ation were evaluated. The DC-photosensitizer polymer appeared to initi ate a cascade addition reaction presumably by adding peroxides and hyd roperoxides to the glucose residues of the dextran carbazate linker. T hese results suggest that this radical formation could propagate down the DC polymer and account for the superior cell killing exhibited by the DC conjugate.