The Role of Molecular Oxygen in the Photodynamic Effect of Phthalocyanines

Abstract

Phthalocyanines are a class of mammalian cell photosensitizers which may be useful in photodynamic therapy for cancer. Chloroaluminum phthalocyanine tetrasulfonate was incubated with Chinese hamster cells in culture and exposed to white light at different concentrations of oxygen. The ability of the cells to form colonies served as an end point for the photobiological effect of the dye. The efficiency of photoinactivation of the sensitized cells decreased with decreasing oxygen concentration. Very little photoinactivation was observed when the atmosphere equilibrated with the cells was oxygen-free nitrogen. At an oxygen partial pressure of 2.5 mm Hg, photoinactivation was reduced by 50% compared to ambient atmosphere. In an attempt to understand the nature of the interaction between excited dyes and oxygen, the ability of several phthalocyanines to photogenerate singlet oxygen was measured. Thus phthalocyanines containing paramagnetic ions (copper, iron, vanadyl) do not generate 1O2 in contradistinction to diamagnetic metals (zinc and aluminum). The latter are efficient photosensitizers, while the former have little if any photobiological activity. In spite of this correlation, singlet oxygen may not be the intermediate involved in cytotoxicity. The reasons are discussed.

The significance of the nature of the photosensitizer for photodynamic therapy: quantitative and biological studies in the colon

“…Other studies (Selman et al, 1986) have shown that both HpD and AlSPc have a similar effect on tumour microcirculation, both appearing to share a final common pathway for the production of tissue damage and vascular occlusion. Although there is conflicting evidence as to whether the mechanism of damage of different photosensitisers is the same and mediated through singlet oxygen (Rosenthal et al, 1986), it is clear from this study that the end biological effect is the same. In particular the important biological advantage of PDT of maintaining the mechanical strength of the colon despite producing full thickness necrosis is not dependent on the photosensitiser used.…”

Evaluation of oxygen dependence on in vitro and in vivo cytotoxicity of photoimmunotherapy using IR-700–antibody conjugates

“…Our prior studies using chemical detection methods for singlet oxygen with sulfonated phthalocyanines substituted with Al, Zn etc, have shown that these PS generate 1 O 2 efficiently with quantum yields ranging between 0.35 – 0.45 [46]. The ability of IR700, a related phthalocyanine dye containing Si, to generate 1 O 2 either alone or as an immunoconjugate was tested in aqueous solution.…”

“…The robust and rapid responses observed with PIT using Ab-IR700 + NIR treatment in cellular and in vivo studies and about 30% protection observed with sodium azide ROS scavengers suggested that mechanisms other than ROS generation, might be responsible for the observed cell necrosis [39,40]. However related phthalocyanine dyes, when evaluated in photochemical and cellular photobiology studies, have been shown to produce 1 O 2 and ROS efficiently and cause cytotoxicity in an oxygen dependent manner [41–46]. A better understanding of the mechanisms underlying the Pan-IR700 mediated PIT will help in using this therapeutic modality efficaciously[47].…”

New medicines and approaches to treatment of atherosclerosis

“…Only those metal complexes with porphyrins and phthalocyanines (a broad class of biologically active substances) that have diamagnetic metals in the inner coordination sphere are capable of undergoing highyield transitions into excited high-spin states (and, consequently, with a high yield of singlet oxygen) [52].…”