Phototoxicity of hydroxymethyl-BODIPYs: are photocages that innocent?†
a
Pierre
Mesdom,
a
Kallol
Purkait,
a
Olivier
Blacque,
b
Arthur H.
Winter,
*c
Kevin
Cariou
*a
and
Gilles
Gasser
*a
Abstract
Photocages are photosensitive molecules that can release specific compounds, usually of biological relevance (e.g., drugs, cellular messengers, etc.), under light irradiation. Along with these compounds, the photocages themselves are putative release byproducts. The (photo-)cytotoxicity of them is hardly known and scarcely studied. To explore these compounds, we synthesized the known BODIPY derivatives commonly used as photocages, i.e., WinterGreen and WinterRed. We investigated in depth their photophysical properties in organic solvents and phosphate buffer. The formation of aggregates by the compounds was analyzed by dynamic light scattering (DLS) and spectral methods, which demonstrated their J-aggregate nature. All compounds exhibited significant phototoxicity in biological assays upon light irradiation at two wavelengths (510 and 645 nm), corresponding to their absorption maxima, in both cancerous (A549) and non-cancerous (RPE-1) cell lines. Investigations into the reactive oxygen species (ROS) generation in organic solutions and intracellularly suggested that the observed phototoxicity might arise via a type I photodynamic therapy (PDT) mechanism. These findings highlight the need for greater scrutiny of photocages themselves in biological studies. Far from being inert carriers, they may exert substantial biological effects, and in some cases, their activity could even surpass that of the released therapeutic agent.
- This article is part of the themed collection: 15th Anniversary: Chemical Science Leading Investigators collection
Please wait while we load your content...
