Project title: Synthetic strategies for photo-sensitizers targeting
Research secondments: University of Amsterdam, BET Solutions
Practical rotation: PorphyChem
Research project description and main objectives: A main topic of POLYTHEA is the development of photosensitizing dyes which are highly specific for and photoactive in the target tissue and can be used for the preparation of formulations, nanomaterials and therapeutic applications.
Thus, this project targets the design and synthesis of tetrapyrrolic bioconjugates for use in photodynamic therapy. The bioconjugate groups will be chosen with regard to tissue uptake and intracellular localization, suitability of linker chemistry and to provide additional therapeutic effects.
For that purpose, unsymmetrically substituted macrocycles will be used and chemically linked with suitable targeting and effector units. This will require the synthesis of amphiphilic macrocycles (for improved membrane passage), that act as light-activated medical agents or imaging devices and have additional effector functions (receptor binding, apoptosis induction, oxygen sensing or delivery, tumor indication, radiotherapy), and have tailor-made photophysical and localization properties. Chemical methods will be developed to link long-chain aliphatics, anti-inflammatory compounds, carbohydrates, anti-angiogenic, and others, to the porphyrin macrocycle. A new class of PS will be based on the use of organic scaffolds, which will be modified in such a way as to carry PS, targeting groups and biological effector groups within one delivery system.
This project has platform character and results thereof can be applied to other research areas which require the elaboration of dye molecules in a spatially and functionally defined manner. Thus, it will interconnect chemistry with the spectroscopic and biological aspect of photodynamic therapy field.
Background: Born in Oxford, UK, Harry undertook his M.Chem. degree at the University of Hull with both B.Sc. and M.Chem. projects under the supervision of Prof. Ross. W. Boyle. Harrys’ M.Chem. project was focused on the synthesis of water-soluble theranostics utilising photodynamic therapy. Along with this, Harry also undertook extracurricular work, funded by the Royal Society of Chemistry, surrounding the use of porphyrins as radiosensitizers. Harrys’ current reading, interests and, synthetic work surround the generation of new long-wavelength-absorbing bio-conjugates for photodynamic therapy.
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