Investigating the photosensitization activities of flavins irradiated by blue LEDs.

Due to their ability to easily absorb light and to generate highly reactive species, photosensitizers emerged as promising tools in a wide variety of physico-chemical and biological processes. Natural photosensitizers have the benefit of a life-compatible toxicological profile. Porphyrins and flavins are such examples that already proved their efficiency as photo-dynamic therapeutics. The present article describes a reliable, easy-to-implement, readily available and reproducible method that can be used to characterize the photosensitizing activity of flavins. Several key factors were investigated during this study, the optimum parameters were: (i) a blue LED light source (λ em = 455 nm) at 6.69 mW; (ii) a pH of 6 mimicking the tumoral environment; (iii) an air-saturated atmosphere reaction medium, (iv) a tetrazolium dye (MTT) was used to monitor the photosensitization efficacy via the generation of the colored MTT-formazan product. This method can be used to rank a series of flavins based on their photosensitizing activities. Such structure-photosensitization activity relationships are essential for the discovery of future potent photosensitizers for photodynamic therapy.

Enhancing the photosensitizing activity of natural flavins: Tuning the heavy-atom effect in the isoalloxazine series.

Structure-photosensitizing activity relationships for a series of flavin analogues were investigated with the final goal of identifying the most potent photosensitizer in these series. The main structural modifications involved the introduction of various halogen atoms in C7- and/or C8-positions on the isoalloxazine ring. These compounds were synthesized by reacting judiciously-functionalized anilines with alloxan. The SAR trends showed that the photosensitizing activity increased with the size of the halogen atoms, confirming the importance of the heavy-atom effect on the photosensitizer's activity. The halogens in C8 were more active than the di-substituted halogens, which in turn were more active than the C7-substituted equivalents. However, even if the photosensitizing activity is slightly less important for the 7- compared to the 8-substituted derivatives, the 7-haloisoalloxazines are promising photosensitizers, as they present a better cellular toxicity profile than the 8-substituted analoges. The photosensitizing activity perfectly correlated with the determined fluorescence for the same compounds. Except for the dihalogeno derivatives, all the compounds were not toxic up to a 50 µM range.

Flavin-Conjugated Nanobombs: Key Structural Requirements Governing Their Self-Assemblies' Morphologies.

In contrast to artificial molecules, natural photosensitizers have the benefit of excellent toxicity profiles and of life-compatible activating energy ranges. Flavins are such photosensitizers that were selected by nature in a plethora of light-triggered biochemical reactions. Flavin-rich nanoparticles could thus emerge as promising tools in photodynamic therapies and in active-targeting drug delivery. Self-assembled flavin-conjugated phospholipids improve the pharmacokinetics of natural flavins and, in the case of controlled morphologies, reduce photobleaching phenomena. The current article presents a proof of concept for the design of riboflavin-rich nanoparticles of tunable morphology from multilamellar patches to vesicular self-assemblies. Coarse-grained simulations of the self-assembling process revealed the key interactions governing the obtained nanomaterials and successfully guided the synthesis of new flavin-conjugates of predictable self-assembly. The obtained flavin-based liposomes had a 65 nm hydrodynamic diameter, were stable, and showed potential photosensitizer activity.