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2019-12-19Zeitschriftenartikel DOI: 10.3390/app10010033
Photodynamic Opening of the Blood−Brain Barrier Using Different Photosensitizers in Mice
Semyachkina-Glushkovskaya, Oxana
Borisova, Ekaterina
Mantareva, Vanya
Angelov, Ivan
Eneva, Ivelina
Terskov, Andrey
Mamedova, Aysel
Shirokov, Alexander cc
Khorovodov, Alexander
Klimova, Maria
Agranovich, Ilana cc
Blokhina, Inna cc
Lezhnev, Nikita
Kurths, Jurgen
Mathematisch-Naturwissenschaftliche Fakultät
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.
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DOI
10.3390/app10010033
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https://doi.org/10.3390/app10010033
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<a href="https://doi.org/10.3390/app10010033">https://doi.org/10.3390/app10010033</a>