Work

Nanolipid Formulations of Benzoporphyrin Derivative: Exploring the Dependence of Nanoconstruct Photophysics and Photochemistry on Their Therapeutic Index in Ovarian Cancer Cells

Year: 2018

Type: article

Abstract: With the rapidly emerging designs and applications of light‐activated, photodynamic therapy (PDT)‐based nanoconstructs, photonanomedicines (PNMs), an unmet need exists to establish whether conventional methods of photochemical and photophysical characterization of photosensitizers are relevant for evaluating new PNMs in order to intelligently guide their design. As a model system, we build on the clinical formulation of benzoporphyrin derivative (BPD), Visudyne®, by developing a panel of nanolipid formulations entrapping new lipidated chemical variants of BPD with differing chemical, photochemical and photophysical properties. These are 16:0 and 20:0 lysophosphocholine‐BPD (16:0/20:0 BPD‐PC), DSPE‐PEG‐BPD and BPD‐cholesterol. We show that Visudyne® was the most phototoxic formulation to OVCAR‐5 cells, and the least effective was liposomal DSPE‐PEG‐BPD. However, these differences did not match their optical, photophysical and photochemical properties, as the static BPD quenching was highest in Visudyne, which also exhibited the lowest generation of singlet oxygen. Furthermore, we establish that OVCAR‐5 cell phototoxicity also does not correlate with rates of photosensitizer photobleaching and fluorescence quantum yields in any nanolipid formulations. These findings warrant critical future studies into subcellular targets and molecular mechanisms of phototoxicity of photodynamic nanoconstructs, as more reliable prognostic surrogates for predicting efficacy to appropriately and intelligently guide their design.

Source: Photochemistry and Photobiology

DOI: 10.1111/php.13002

Authors: Girgis Obaid, Wendong Jin, Shazia Bano, David Kessel, Tayyaba Hasan