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酞菁光敏剂对朊病毒光动力灭活的优化:单线态氧的关键作用。

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

作者信息

Kostelanska Marie, Freisleben Jaroslav, Backovska Hanusova Zdenka, Mosko Tibor, Vik Robert, Moravcova Daniela, Hamacek Ales, Mosinger Jiri, Holada Karel

机构信息

Institute of Immunology and Microbiology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.

Regional Innovation Centre for Electrical Engineering, Faculty of Electrical Engineering, University of West Bohemia, Pilsen, Czech Republic.

出版信息

J Biophotonics. 2019 Aug;12(8):e201800340. doi: 10.1002/jbio.201800430. Epub 2019 May 2.

DOI:10.1002/jbio.201800430
PMID:30989822
Abstract

Prion disorders are fatal neurodegenerative diseases caused by the autocatalytic conversion of a natively occurring prion protein (PrP ) into its misfolded infectious form (PrP ). The proven resistance of PrP 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(SO ) ) utilizing two custom-built red light sources. The treatment eliminates PrP 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 (O ( Δ )) is the only species significantly photogenerated by AlPcOH(SO ) , and it is responsible for the PDI of prions. More intensive light conditions show not only higher O ( Δ ) production but also decreases in AlPcOH(SO ) photostability. Our findings suggest that PDI by AlPcOH(SO ) -generated O ( Δ ) represents a promising approach for prion inactivation that may be useful in future decontamination strategies for delicate medical tools.

摘要

朊病毒疾病是由天然存在的朊病毒蛋白(PrP )自催化转化为错误折叠的感染性形式(PrP )引起的致命性神经退行性疾病。已证实PrP对常规消毒程序具有抗性,这增加了在医疗环境中朊病毒传播的风险。在此,我们展示了利用两种定制的红光光源,二磺酸化羟基铝酞菁(AlPcOH(SO ) )对朊病毒进行有效的光动力灭活(PDI)。该处理可消除感染性小鼠脑匀浆中的PrP信号,其效率取决于光强度,但对总蛋白含量影响较小。重要的是,单线态氧(O ( Δ ))是AlPcOH(SO ) 唯一显著光生成的物质,它是朊病毒PDI的原因。更强的光照条件不仅显示出更高的O ( Δ )生成量,还会降低AlPcOH(SO ) 的光稳定性。我们的研究结果表明,由AlPcOH(SO ) 产生的O ( Δ )进行的PDI代表了一种有前景的朊病毒灭活方法,可能在未来用于精密医疗工具的去污策略中。

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