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

Abstract

Prion disorders are fatal neurodegenerative diseases caused by the autocatalytic conversion of a natively occurring prion protein (PrP^C ) into its misfolded infectious form (PrP^TSE ). The proven resistance of PrP^TSE 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 PrP^TSE 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 (¹ Δ_g )) 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 (¹ Δ_g ) production but also decreases in AlPcOH(SO₃ )₂ photostability. Our findings suggest that PDI by AlPcOH(SO₃ )₂ -generated O₂ (¹ Δ_g ) represents a promising approach for prion inactivation that may be useful in future decontamination strategies for delicate medical tools.

Keywords: decontamination; photodynamic inactivation; phthalocyanines; prions; singlet oxygen.