Project R-13560

Rational design, synthesis, and photophysics of heavy-atom-free, dual-functioning, near-infrared BODIPY photosensitizers (Research)

Photodynamic therapy (PDT) has become part of the wider toolbox in the battle against cancer. It is minimally invasive and presents reduced complications as compared to chemotherapy or surgery. PDT involves a photosensitizer, which upon irradiation gets excited and generates cytotoxic reactive oxygen species (e.g. singlet oxygen) that damage cancer cells. Boron dipyrromethene (BODIPY) dyes represent a particular class within the broad array of potential photosensitizers. Their highly fluorescent nature opens the door for theranostic applications, combining imaging and therapy using a single, easily synthesized chromophore. However, near-infrared absorption is strongly desired for PDT to enhance tissue penetration. Furthermore, reactive oxygen species should preferentially be generated without the incorporation of heavy atoms, as these often require additional synthetic efforts and/or afford dark cytotoxicity. Solutions for both problems are known, but it remains a challenge to combine these properties in one simple BODIPY material. In this Ph.D. project, we target a series of rationally (computationally) designed, innovative BODIPY photosensitizers, active in the phototherapeutic window and showing balanced brightness and phototoxic power. Chromophore synthesis efforts will be complemented by advanced (time-resolved) spectroscopy studies to unravel the excited state dynamics and to apply the generated insights for improved structural designs. Implementation of the most promising dual-functioning photosensitizers in dedicated nanocarriers and cell tests will then enable us to take the next step toward final in vivo analysis and implementation in clinical protocols.

01 November 2022 - 31 October 2026