A comparative study of photosensitizers with and without carbohydrate moieties

Many potentially useful photosensitizers for the photodynamic therapy (PDT) of malignancies have poor tumor selectivity. We hypothesized that certain carbohydrates on conjugating with photosensitizers at the optimal position will produce carbohydrate receptor specific photosensitizers with enhanced PDT efficacy and tumor selectivity. In order to test our hypothesis, my research project is divided in three parts.; In the first part of the project, attempts were directed towards the synthesis of carbohydrate conjugates of 3-(1-hexyloxyethyl)-3-devinyl-pyropheophorbide- a (HPPH). Although there was no direct evidence to support that HPPH-carbohydrate conjugates were targeting the carbohydrate recognition proteins (e.g. galectins), the higher tumor uptake and less skin phototoxicity strongly suggested that these conjugates have enhanced tumor specificity.; The second part of my research project was aimed to extend the approach established in our laboratory to further investigate the effect of the presence and position of various carbohydrate moieties on the purpurinimide system. In this approach, the carbohydrate moieties were regioselectively introduced at different peripheral positions and/or with different types of linkers. Interestingly, among a series of analogs, the conjugate containing a lactose moiety at position-3 of the purpurinimide system was found to be most effective.; Part three of my research project was focused on long wavelength photosensitizers for the treatment of large tumor and deeply embedded tumors. After in vitro phototoxicity screening of a series of bacteriopyropheophorbide- a analogs with different length alky1 ether chains, with and without additional keto-group and their palladium and zinc complex, the n-hexy1 derivative of bacteriopyropheophorbide-a was selected and coupled with the galactose moiety. Preliminary in vitro results showed that the carbohydrate conjugate of bacteriochlorin had better PDT efficacy than corresponding non-conjugate analog. However, these results are very preliminary and further detailed in vitro and in vivo studies are required to determine the utility of these candidates.; In an additional study it was observed that most of the carbohydrate conjugates synthesized in this project were not the substrates of the BCRP transporter, therefore, these carbohydrate analogs can overcome the BCRP based drug resistance. (Abstract shortened by UMI.)...