Thionine in the design of new photosensitizers: Bromination and vehiculization in polymeric nanoparticles

Abstract

To face the challenges of optimizing the properties of the photosensitizers currently used in the photodynamic inactivation of various microorganisms, we propose the bromination of thionine and the use of polymeric nanoparticles for the entrapment of halogenated derivative. Within this framework, the dibrominated derivative of thionine was synthesized and characterized. This new compound showed a high chemical and photochemical stability. In addition, bromination decreased the ionization constant and increased the aggregation of this photosensitizer in an aqueous medium. For this reason, the new compound showed a lower quantum yield of singlet oxygen production. However, the dibrominated thionine showed greater cell damage after photodynamic treatment. In order to prevent or decrease the aggregation of the photosensitizer in an aqueous medium, it was vehiculized in different polymeric polyacrylamide nanoparticles. In general, the vehiculization of the photosensitizers (PSs) in nanosized systems increased the production of singlet oxygen and enhanced their phototoxic activity against the microorganisms evaluated (methicillin-sensitive Staphylococcus aureus and methicillin resistant Staphylococcus aureus). The nanoparticle formed with the monomer 2 hydroxyethyl methacrylate(HEMA) showed the best photodynamic efficacy. The results obtained clearly suggest that polyacrylamide nanoparticles loaded with photosensitizers of the thiazine family have great potential for further application in antimicrobial photodynamic therapy.