Novel porphyrin conjugates with a potent photodynamic antitumor effect: differential efficacy of mono- and bis-beta-cyclodextrin derivatives in vitro and in vivo
Language English Country United States Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- beta-Cyclodextrins pharmacology MeSH
- Cell Death drug effects radiation effects MeSH
- Time Factors MeSH
- Photosensitizing Agents pharmacology MeSH
- Dermatitis, Phototoxic drug therapy MeSH
- Skin drug effects radiation effects MeSH
- Humans MeSH
- Lysosomes pathology MeSH
- Mice, Inbred BALB C MeSH
- Mice MeSH
- Tumor Cells, Cultured MeSH
- Porphyrins pharmacology MeSH
- Antineoplastic Agents pharmacology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- beta-Cyclodextrins MeSH
- Photosensitizing Agents MeSH
- Porphyrins MeSH
- Antineoplastic Agents MeSH
In the present study we investigated the photosensitizing properties of two novel mono- and bis-cyclodextrin tetrakis (pentafluorophenyl) porphyrin derivatives in several tumor cell lines and in BALB/c mice bearing subcutaneously transplanted syngeneic mouse mammary carcinoma 4T1. Both studied sensitizers were localized mainly in lysosomes and were found to induce cell death by triggering apoptosis in human leukemic cells HL-60. In 4T1 and other cell lines both apoptotic and necrotic modes of cell death occurred depending on drug and light doses. Mono-cyclodextrin porphyrin derivative P(beta-CD)1 exhibited stronger in vitro phototoxic effect than bis-cyclodextrin derivative P(beta-CD)2. However, in vivo P(beta-CD)2 displayed faster tumor uptake with maximal accumulation 6 h after application, leading to complete and prolonged elimination of subcutaneous tumors within 3 days after irradiation (100 J cm(-2)). In contrast, P(beta-CD)1 uptake was slower (48 h) and the reduction of tumor mass was only transient, reaching the maximum at the 12 h interval when a favorable tumor-to-skin ratio appeared. Thus, P(beta-CD)2 represents a new photosensitizing drug displaying fast and selective tumor uptake, strong antitumor activity and fast elimination from the body.
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