Optimization of the photodynamic inactivation of prions by a phthalocyanine photosensitizer: The crucial involvement of singlet oxygen

Prion disorders are fatal neurodegenerative diseases caused by the autocatalytic conversion of a natively occurring prion protein (PrPC) into its misfolded infectious form (PrPTSE). The proven resistance of PrPTSE to common disinfection procedures increases the risk of prion transmission in medical settings. Herein, we present the effective photodynamic inactivation (PDI) of prions by disulfonated hydroxyaluminum phthalocyanine (AlPcOH(SO3)2) utilizing two custom‐built red light sources. The treatment eliminates PrPTSE signal in infectious mouse brain homogenate with efficiency that depends on light intensity but has a low effect on the overall protein content. Importantly, singlet oxygen (O2(1Δg)) is the only species significantly photogenerated by AlPcOH(SO3)2, and it is responsible for the PDI of prions. More intensive light conditions show not only higher O2(1Δg) production but also decreases in AlPcOH(SO3)2 photostability. Our findings suggest that PDI by AlPcOH(SO3)2‐generated O2(1Δg) represents a promising approach for prion inactivation that may be useful in future decontamination strategies for delicate medical tools. The PDI of prions by AlPcOH(SO3)2 using two custom‐built red light sources revealed the exponential course of PrPTSE signal elimination in infectious mouse brain homogenate with a low effect on its overall protein content. The causative agent, O2(1Δg), was the only species significantly photogenerated by AlPcOH(SO3)2, and it was responsible for the PDI of prions. The findings represent a promising approach for prion inactivation that may be useful in future decontamination strategies of delicate medical tools.