Molecular and Formulation Strategies for Photosensitizer Design

Targeted delivery and selective activation of photosensitizers (PSs) is a fundamental aim in the design of photosensitizers. Ideally, the desired properties should be imprinted in the molecular structure during the design process. A combination of molecular functionalization, conformational design, linking to solubilizing agents and incorporation of singlet oxygen trapping moieties was used in synthetic organic chemistry photosensitizer methods development. We show that: a) the molecular shape of a drug is important for cell internalization and controlling triplet state formation, b) macrocycle distortion can be used to modulate the photophysical parameters, c) singlet oxygen trapping units are suitable for controlled release of 1O2, and d) that incorporation of PSs into hydrogels facilitates a PDT-induced response of the immune system. Molecular design in organic synthesis can be used to develop new classes of photosensitizers with improved uptake, targeting, and PDT properties.