Abstract
We report the synthesis, spectroscopic properties and intracellular imaging of recombinant antibody single chain fragment (scFv) conjugates with photosensitizers used for photodynamic therapy of cancer (PDT). Two widely-studied photosensitizers have been selected: preclinical pyropheophorbide-a (PPa) and verteporfin (VP), which has been clinically approved for the treatment of acute macular degeneration (Visudyne®). Pyropheophorbide-a and verteporfin have been conjugated to an anti-HER2 scFv containing on average ten photosensitizer molecules per scFv with a small contribution (≤20%) from non-covalently bound molecules. Confocal fluorescence microscopy demonstrates good cellular uptake of PPa conjugate with the HER2-positive cell line, SKOV-3, while negligible cell uptake is demonstrated for the HER2-negative cell line, KB. For the VP conjugate, increased rate of cellular uptake and prolonged retention in SKOV-3 cells is observed compared to free photosensitizer. In clinical applications this could provide increased potency and desired selectivity towards malignant tissue, leaving surrounding healthy tissue unharmed and reducing skin photosensitivity. The present study highlights the usefulness of photosensitizer immunoconjugates with scFvs for targeted PDT.
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This paper was published as part of the special issue in honour of David Phillips.
Electronic supplementary information (ESI) available: Additional imaging data. See DOI: 10.1039/b708320c
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Kuimova, M.K., Bhatti, M., Deonarain, M. et al. Fluorescence characterisation of multiply-loaded anti-HER2 single chain Fv-photosesitizer conjugates suitable for photodynamic therapy. Photochem Photobiol Sci 6, 933–939 (2007). https://doi.org/10.1039/b708320c
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DOI: https://doi.org/10.1039/b708320c