PHOTOPROPERTIES OF A MESOCHLORIN E6-N-(2-HYDROXYPROPYL)METHACRYLAMIDE COPOLYMER CONJUGATE

In the photodynamic therapy (PDT) of tumors, improved efficiency of photosensitizer delivery to tumor cells and tumors can sometimes be obtained by binding them to monoclonal antibodies or other proteins, particulate materials, and certain types of synthetic water soluble polymers. Synthetic polymers are of particular interest as drug delivery carriers since targeting groups specific for surface markers on tumor cells can be attached to the polymer backbone increase the cellular uptake via receptor-mediated endocytosis. However, in many cases, the binding of sensitizers to macromolecules significantly alters their spectral and photosensitizing properties. This paper describes the effects of covalently binding the photosensitizer, mesochlorin e6 monoethylenediamine (CM), to a model N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer on its spectral, photophysical, photosensitizing and photobleaching properties in aqueous solution. Binding had little effect on the spectrum or triplet lifetime of CM, but significantly decreased the bimolecular quenching constant of oxygen for the chlorin triplet. Binding also reduced the quantum yield of singlet oxygen production by illuminated CM from 0.73 to 0.25. Photo-oxidation efficiencies for furfuryl alcohol and certain biomolecules were also decreased. Addition of a cationic detergent to the CM-HPMA copolymer increased the yield of singlet oxygen production and the photosensitizing efficiency up to the levels of the free sensitizer. Binding CM to the HPMA copolymer significantly increased its resistance to photobleaching.