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  Photodynamic opening of the blood–brain barrier using different photosensitizers in mice

Semyachkina-Glushkovskaya, O., Borisova, E., Mantareva, V., Angelov, I., Eneva, I., Terskov, A., Mamedova, A., Shirokov, A., Khorovodov, A., Klimova, M., Agranovich, I., Blokhina, I., Lezhnev, N., Kurths, J. (2020): Photodynamic opening of the blood–brain barrier using different photosensitizers in mice. - Applied Sciences, 10, 1, 33.
https://doi.org/10.3390/app10010033

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Semyachkina-Glushkovskaya, Oxana1, Author
Borisova, Ekaterina1, Author
Mantareva, Vanya1, Author
Angelov, Ivan1, Author
Eneva, Ivelina1, Author
Terskov, Andrey1, Author
Mamedova, Aysel1, Author
Shirokov, Alexander1, Author
Khorovodov, Alexander1, Author
Klimova, Maria1, Author
Agranovich, Ilana1, Author
Blokhina, Inna1, Author
Lezhnev, Nikita1, Author
Kurths, Jürgen2, Author              
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1External Organizations, ou_persistent22              
2Potsdam Institute for Climate Impact Research, ou_persistent13              

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 Abstract: In a series of previous studies, we demonstrated that the photodynamic therapy (PDT), as a widely used tool for treatment of glioblastoma multiforme (GBM), also site-specifically opens the blood–brain barrier (BBB) in PDT-dose and age-related manner via reversible disorganization of the tight junction machinery. To develop the effective protocol of PDT-opening of the BBB, here we answer the question of what kind of photosensitizer (PS) is the most effective for the BBB opening. We studied the PDT-opening of the BBB in healthy mice using commercial photosensitizers (PSs) such as 5-aminolevulenic acid (5-ALA), aluminum phthalocyanine disulfonate (AlPcS), zinc phthalocyanine (ZnPc) and new synthetized PSs such as galactose functionalized ZnPc (GalZnPc). The spectrofluorimetric assay of Evans Blue albumin complex (EBAC) leakage and 3-D confocal imaging of FITC-dextran 70 kDa (FITCD) extravasation clearly shows a revisable and dose depended PDT-opening of the BBB to EBAC and FITCD associated with a decrease in presence of tight junction (TJ) in the vascular endothelium. The PDT effects on the BBB permeability, TJ expression and the fluorescent signal from the brain tissues are more pronounced in PDT-GalZnPc vs. PDT-5-ALA/AlPcS/ZnPc. These pre-clinical data are the first important informative platform for an optimization of the PDT protocol in the light of new knowledge about PDT-opening of the BBB for drug brain delivery and for the therapy of brain diseases. View Full-Text

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 Dates: 2019-12-172020-01
 Publication Status: Finally published
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 Rev. Type: Peer
 Identifiers: DOI: 10.3390/app10010033
PIKDOMAIN: RD4 - Complexity Science
Organisational keyword: RD4 - Complexity Science
MDB-ID: No data to archive
Working Group: Network- and machine-learning-based prediction of extreme events
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Title: Applied Sciences
Source Genre: Journal, SCI, Scopus, oa
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Pages: - Volume / Issue: 10 (1) Sequence Number: 33 Start / End Page: - Identifier: Other: MDPI AG
Other: 2076-3417
CoNE: https://publications.pik-potsdam.de/cone/journals/resource/applied-sciences
Publisher: MDPI