Modification of the structure of a porphyrin dye shows a significant change in the rate of charge recombination between injected electrons in the TiO2 and the oxidized dye anchored to it following optical excitation, offering an insight into fundamental understanding of processes occurring at the dye/semiconductor interface.

Current photodynamic therapy (PDT) of cancer is limited by inefficiencies involved in specifically targeting photosensitizers to tumors. Although antibodies are being explored as targeting vehicles, they present significant challenges, particularly in terms of pharmacokinetics and drug-coupling. We describe here a novel and effective system to covalently attach multiple photosensitizer molecules (both preclinical, pyropheophorbide-a and clinically approved, verteporfin photosensitizers) to single-chain Fvs. Further, we demonstrate that not only do the resulting photoimmunoconjugates retain photophysical functionality, they are more potent than either free photosensitizer, effectively killing tumor cells in vitro and in vivo. For example, treatment of human breast cancer xenografts with a photoimmunoconjugate comprising an anti-HER-2 scFv linked to 8-10 molecules of pyropheophorbide-a leads to significant tumor regression. These results give an insight into the important features that make scFvs good carriers for PDT drugs and provide proof of concept of our unique approach to targeted photodynamic therapy (tPDT). This promises to significantly improve on current photodynamic therapies for the treatment of cancer. ' 2007 Wiley-Liss, Inc.Key words: photodynamic therapy; single chain Fv; pyropheophorbide-a; verteporfin Photodynamic therapy (PDT) is a minimally invasive procedure used in a range of conditions where superficially localized lesions such as age-related macular degeneration (AMD) or tumors need to be treated. 1 PDT is typically a 2-step process that involves the administration of a photosensitizer (PS) leading to marginal accumulation in the tumor. Following this, the PS is activated by exposure to light of an appropriate wavelength. This ultimately leads to the conversion of molecular oxygen into reactive oxygen species (ROS), primarily singlet oxygen, leading to tumor cell death via irreversible damage to cellular components such as proteins, lipids and DNA. 2 Current clinical use of PDT achieves efficacies similar to conventional therapies but with lower morbidity, simplicity of use and improved functional and cosmetic outcome. 3,4 PDT has mainly been used where conventional approaches have failed or were unsuitable. These include premalignant dysplastic lesions and noninvasive cancers, which are commonly found in the mucosa of the aerodigestive 5 and urinary tracts. 6 Success in treating these types of cancers has been achieved using Photofrin 1 , 7 Levulan 18 and Foscan 1 . 9 The most successful application of PDT has been for wet age-related macular degeneration (AMD) for which the photosensitizer verteporfin (Visudyne 1 ) has been used to destroy ocular neovasculature. 10 PDT has also had great successes in dermatology because of its impressive cosmetic outcome. Methyl 5-aminolaevulinate (Metvix 1 ) has been used to treat actinic keratosis with up to 90% cure. 11 Although PSs accumulate in cancer cells, the tumor specificity ratios are low and their inherent hydrophobicity, causes them to persist...

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