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- W2002804476 abstract "Photodynamic therapy (PDT) is a targeted treatment modality where photosensitizers accumulate into cells and are selectively activated by light leading to the production of toxic species and cell death. Focusing the action of photosensitizers to a unique intracellular target may enhance their cytotoxicity. In this study, we demonstrate that the routing of the porphyrin-based photosensitizer chlorin e6, to the nucleus of cells can significantly alter its toxicity profile. The cellular localization of chlorin e6 was achieved by coupling the chromophore during solid-phase synthesis to a nucleus-directed linear peptide (Ce6-peptide) or a branched peptide (Ce6-loligomer) composed of eight identical arms displaying the sequence of the Ce6-peptide. These constructs incorporated signals guiding their cytoplasmic uptake and nuclear localization. Ce6-peptide and Ce6-loligomer displayed an enhanced photodynamic activity compared to unconjugated chlorin e6, lowering the observed CD50 values for CHO and RIF-1 cells by 1 or more orders of magnitude. The intracellular accumulation of Ce6-peptide and Ce6-loligomer was assessed by electron and confocal microscopy as well as by flow cytometry. Constructs were internalized by cells within an hour and by 6 h, the release of active oxygen species could be observed within the nucleus of cells pretreated with Ce6-loligomer. These results highlight the utility of designing peptides as vehicles for regulating the intracellular distribution of photosensitizers such as chlorin e6 in order to maximize their efficacy in PDT." @default.
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- W2002804476 date "1999-10-16" @default.
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- W2002804476 title "Potentiation of Chlorin e6 Photodynamic Activity in Vitro with Peptide-Based Intracellular Vehicles" @default.
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- W2002804476 doi "https://doi.org/10.1021/bc990020u" @default.
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