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The new sensitizing agents for photodynamic therapy: 21-selenaporphyrin and 21-thiaporphyrin
E Marcinkowska1, P Ziółkowski, E Pacholska
1Department of Tumor Immunology, Polish Academy of Sciences, Wrocław, Poland.
Background:
Photodynamic therapy may be a promising treatment for patients with tumors. The mechanism of its action is poorly understood and different from the cytotoxic effects induced by antitumor drugs.
Materials And Methods:
New sensitizers, termed as 21-selenaporphyrin (SEP) and 21-thiaporphyrin (STSP) were studied for their photocytotoxicity in vitro against selected human cancer cell lines. This study was followed by in vivo screening of the effect of SEP using an animal tumor model. The activity of the new agents was compared with that of a known photosensitizer, namely chlorin e6. In our selection of the cell lines applied for in vitro study, the possible accessibility and effectiveness of photodynamic therapy (PDT) for treatment of colon and urinary bladder cancers, was considered.
Results:
New compounds appeared to be not toxic for tested cells in culture, without exposure to light. The STSP exerted in vitro effects comparable with chlorin e6 photocytotoxicity, while SEP appeared to be ineffective. However, in vivo experiments performed in a BFS1 fibrosarcoma tumor model in mice showed that the SEP was at least as much effective as chlorin e6 in the induction of tumor necrosis. In contrast to chlorin e6, SEP-PDT induced no skin sensitization.
Conclusions:
Both new sensitizers can be applied in PDT at no risk of skin damage. The mechanism of the action of these two compounds is probably different, i.e. the 21-thiaporphyrin possibly acts directly on tumor cells and the 21-selenaporphyrin via endothelial cells of newly formed tumor vasculature.
Insights
New photosensitizers, 21-selenaporphyrin (SEP) and 21-thiaporphyrin (STSP), show promise for photodynamic therapy (PDT). SEP demonstrated in vivo efficacy without skin sensitization, suggesting potential for tumor treatment.
Area of Science:
- Photodynamic therapy
- Cancer research
- Medicinal chemistry
Background:
- Photodynamic therapy (PDT) is a potential cancer treatment, but its mechanisms are not fully understood.
- Existing antitumor drugs have cytotoxic effects distinct from PDT.
Purpose of the Study:
- To evaluate the photocytotoxicity of novel sensitizers, 21-selenaporphyrin (SEP) and 21-thiaporphyrin (STSP), against human cancer cell lines.
- To assess the in vivo efficacy of SEP in an animal tumor model.
- To compare the activity of SEP and STSP with a known photosensitizer, chlorin e6.
Main Methods:
- In vitro photocytotoxicity assays using human cancer cell lines.
- In vivo studies utilizing a BFS1 fibrosarcoma tumor model in mice.
- Comparison of novel sensitizers with chlorin e6.
Main Results:
- SEP and STSP were non-toxic to cells in culture without light exposure.
- STSP showed in vitro photocytotoxicity comparable to chlorin e6.
- SEP was ineffective in vitro but demonstrated significant in vivo tumor necrosis induction, similar to chlorin e6.
- SEP-PDT did not induce skin sensitization, unlike chlorin e6.
Conclusions:
- Both SEP and STSP can be used in PDT without causing skin damage.
- The mechanisms of action likely differ: STSP may target tumor cells directly, while SEP might act on tumor vasculature endothelial cells.