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Home > Technology > Technology cont.d TechnologyFor PDT to reach its full therapeutic potential in cancer and other indications, it is important to improve on the photophysical and targeting performances of first generation sensitisers (e.g., porfimer sodium). PhotoBiotics has achieved both of these goals by discovering new and better ways to target the photosensitiser, and creating new photosensitisers capable of activation at longer light wavelengths. This ensures light penetrates more deeply into dense body tissues, enabling PDT to access and destroy a greater range of tumours. So-called second-generation PDT drugs, which are designed to address some of these issues, are already in clinical trials in cancer and other indications. PhotoBiotics' strategy is to make significant improvements focussed initially upon cancer and later on other indications. There have been attempts to improve sensitiser targeting by attaching them to large protein-based molecules (LPM: 150 Kda). This has so far not proved to be a successful strategy because LPMs are often damaged by the photosensitiser chemical conjugation process, resulting in weakened binding activity to the target tumour. In addition, only 1-2 photosensitiser molecules are ever successfully attached to these LPM's, resulting in a low dose of PDT photosensitiser being delivered to the tumour. The size of the LPM relative to the photosensitiser also leads to problems of quenching the photoactivity by bimolecular processes, and the photosensitiser is physically separated from its target by the LPM, so reducing photosensitiser effectiveness. The PhotoBiotics' team has successfully overcome these difficulties by using distinctive and patented biotechnology, developed in-house at Imperial College, which allows for multi-functionalisation of much smaller protein-based targeting agents. Not only are the PhotoBiotics team demonstrating much better targeting compared to ordinary PDT, but results indicate significantly improved tumour cell killing in vivo. In addition, the efficacy and potency of some current 2nd generation PDT sensitisers has also been shown to significantly improve when delivered to target cells via PhotoBiotics' patented targeting technology. In attempting to shift the wavelength of light absorption by porphyrin-based photosensitisers further into the red and near infra-red (for deeper penetration into the body), there is a limitation to how far towards the infra-red one can go. This is because the energy of the photosensitiser triplet state (needed for the generation of the cytotoxic species, singlet oxygen) progressively drops, and eventually is not sufficient to generate singlet oxygen, which is the cytotoxic and photonecrotic agent. This limitation may be overcome by the use of new photosensitisers and advanced laser-physical techniques and PhotoBiotics is already developing the relevant technologies.
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