Optimal photosensitizers for photodynamic therapy : the preparation and characterization of novel photosensitizers derived from mesoporphyrin

Doctoral Thesis

Porphyrins are essential in living organisms. E.g. in the red oxygen carrying blood protein hemoglobin oxygen binds to the Fe2+-containing heme and in plants the green pigment chlorophyll is responsible for the initial steps in photosynthesis. The absorption of light by a porphyrin, followed by energy transfer to oxygen can lead to the formation of highly toxic but short living singlet oxygen. When such a porphyrin localizes in a tumor it is possible to destroy the tumor locally by the irradiating it with light. This treatment is known as photodynamic therapy and the pigment is called a photosensitizer. However a major drawback of current photosensitizers is that they do not show strong absorption in the far-red part of the spectrum where light penetrates tissue optimal. Besides patients treated with these photosensitizers remain light sensitive for 3-8 weeks. This thesis describes the preparation of new photosensitizers with strong absorption of light at 680-690 nm. The preparation...Show morePorphyrins are essential in living organisms. E.g. in the red oxygen carrying blood protein hemoglobin oxygen binds to the Fe2+-containing heme and in plants the green pigment chlorophyll is responsible for the initial steps in photosynthesis. The absorption of light by a porphyrin, followed by energy transfer to oxygen can lead to the formation of highly toxic but short living singlet oxygen. When such a porphyrin localizes in a tumor it is possible to destroy the tumor locally by the irradiating it with light. This treatment is known as photodynamic therapy and the pigment is called a photosensitizer. However a major drawback of current photosensitizers is that they do not show strong absorption in the far-red part of the spectrum where light penetrates tissue optimal. Besides patients treated with these photosensitizers remain light sensitive for 3-8 weeks. This thesis describes the preparation of new photosensitizers with strong absorption of light at 680-690 nm. The preparation of these porphyrin derivatives takes place via unprecedented chemical reactions and an explanation for the chemistry involved is given. Tests on mice showed that the lifetime of these new porphyrin derivatives in their body is reduced to less then 3 days, which makes them very interesting candidates as new generation photosensitizers for photodynamic therapyShow less

Biological activity

Chlorins