Low-Level Laser Treatment Induces the Blood-Brain Barrier Opening and the Brain Drainage System Activation: Delivery of Liposomes into Mouse Glioblastoma

Oxana Semyachkina-Glushkovskaya; Denis Bragin; Olga Bragina; Sergey Socolovski; Alexander Shirokov; Ivan Fedosov; Vasily Ageev; Inna Blokhina; Alexander Dubrovsky; Valeria Telnova; Andrey Terskov; Alexander Khorovodov; Daria Elovenko; Arina Evsukova; Maria Zhoy; Ilana Agranovich; Elena Vodovozova; Anna Alekseeva; Jürgen Kurths; Edik Rafailov

doi:10.3390/pharmaceutics15020567

Low-Level Laser Treatment Induces the Blood-Brain Barrier Opening and the Brain Drainage System Activation: Delivery of Liposomes into Mouse Glioblastoma

Oxana Semyachkina-Glushkovskaya, Denis Bragin, Olga Bragina, Sergey Socolovski, Alexander Shirokov, Ivan Fedosov, Vasily Ageev, Inna Blokhina, Alexander Dubrovsky, Valeria Telnova, Andrey Terskov, Alexander Khorovodov, Daria Elovenko, Arina Evsukova, Maria Zhoy, Ilana Agranovich, Elena Vodovozova, Anna Alekseeva, Jürgen Kurths, Edik Rafailov

Research output: Contribution to journal › Article › peer-review

Abstract

The progress in brain diseases treatment is limited by the blood-brain barrier (BBB), which prevents delivery of the vast majority of drugs from the blood into the brain. In this study, we discover unknown phenomenon of opening of the BBBB (BBBO) by low-level laser treatment (LLLT, 1268 nm) in the mouse cortex. LLLT-BBBO is accompanied by activation of the brain drainage system contributing effective delivery of liposomes into glioblastoma (GBM). The LLLT induces the generation of singlet oxygen without photosensitizers (PSs) in the blood endothelial cells and astrocytes, which can be a trigger mechanism of BBBO. LLLT-BBBO causes activation of the ABC-transport system with a temporal decrease in the expression of tight junction proteins. The BBB recovery is accompanied by activation of neuronal metabolic activity and stabilization of the BBB permeability. LLLT-BBBO can be used as a new opportunity of interstitial PS-free photodynamic therapy (PDT) for modulation of brain tumor immunity and improvement of immuno-therapy for GBM in infants in whom PDT with PSs, radio- and chemotherapy are strongly limited, as well as in adults with a high allergic reaction to PSs.

Original language	English
Article number	567
Number of pages	21
Journal	Pharmaceutics
Volume	15
Issue number	2
Early online date	8 Feb 2023
DOIs	https://doi.org/10.3390/pharmaceutics15020567
Publication status	Published - 8 Feb 2023

Bibliographical note

Copyright © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

Funding: S.-G.O., I.F., A.S., I.B., A.K., A.T., D.E., V.A., A.E., M.Z., V.A. and A.D. were supported by Grant from the Russian Ministry of Science and High EducationNo 075-15-2022-1094; A.S. and A.K. were supported by Grant from RSF No 21-75-10088; 23-25-00296. D.B. was supported by NIH
R21NS091600 and R01NS112808. E.R. and S.S. gratefully acknowledge funding from EU’s H2020 FET OPEN NEUROPA project under the Grant Agreement No. 863214. E.V. and A.A. were supported by Grant from RSF No 21-74-20177 in part of the synthesis of fluorescently labeled liposomes.

Keywords

blood-brain barrier
brain drainage system
glioblastoma
infrared low-intensity laser treatment
liposomes

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SemyachkinaGlushkovskayaetal_2023_VoR
Copyright © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Final published version, 4.6 MBLicence: CC BY 4.0

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Semyachkina-Glushkovskaya, O., Bragin, D., Bragina, O., Socolovski, S., Shirokov, A., Fedosov, I., Ageev, V., Blokhina, I., Dubrovsky, A., Telnova, V., Terskov, A., Khorovodov, A., Elovenko, D., Evsukova, A., Zhoy, M., Agranovich, I., Vodovozova, E., Alekseeva, A., Kurths, J., & Rafailov, E. (2023). Low-Level Laser Treatment Induces the Blood-Brain Barrier Opening and the Brain Drainage System Activation: Delivery of Liposomes into Mouse Glioblastoma. Pharmaceutics, 15(2), Article 567. https://doi.org/10.3390/pharmaceutics15020567

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abstract = "The progress in brain diseases treatment is limited by the blood-brain barrier (BBB), which prevents delivery of the vast majority of drugs from the blood into the brain. In this study, we discover unknown phenomenon of opening of the BBBB (BBBO) by low-level laser treatment (LLLT, 1268 nm) in the mouse cortex. LLLT-BBBO is accompanied by activation of the brain drainage system contributing effective delivery of liposomes into glioblastoma (GBM). The LLLT induces the generation of singlet oxygen without photosensitizers (PSs) in the blood endothelial cells and astrocytes, which can be a trigger mechanism of BBBO. LLLT-BBBO causes activation of the ABC-transport system with a temporal decrease in the expression of tight junction proteins. The BBB recovery is accompanied by activation of neuronal metabolic activity and stabilization of the BBB permeability. LLLT-BBBO can be used as a new opportunity of interstitial PS-free photodynamic therapy (PDT) for modulation of brain tumor immunity and improvement of immuno-therapy for GBM in infants in whom PDT with PSs, radio- and chemotherapy are strongly limited, as well as in adults with a high allergic reaction to PSs.",

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author = "Oxana Semyachkina-Glushkovskaya and Denis Bragin and Olga Bragina and Sergey Socolovski and Alexander Shirokov and Ivan Fedosov and Vasily Ageev and Inna Blokhina and Alexander Dubrovsky and Valeria Telnova and Andrey Terskov and Alexander Khorovodov and Daria Elovenko and Arina Evsukova and Maria Zhoy and Ilana Agranovich and Elena Vodovozova and Anna Alekseeva and J{\"u}rgen Kurths and Edik Rafailov",

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Semyachkina-Glushkovskaya, O, Bragin, D, Bragina, O, Socolovski, S, Shirokov, A, Fedosov, I, Ageev, V, Blokhina, I, Dubrovsky, A, Telnova, V, Terskov, A, Khorovodov, A, Elovenko, D, Evsukova, A, Zhoy, M, Agranovich, I, Vodovozova, E, Alekseeva, A, Kurths, J & Rafailov, E 2023, 'Low-Level Laser Treatment Induces the Blood-Brain Barrier Opening and the Brain Drainage System Activation: Delivery of Liposomes into Mouse Glioblastoma', Pharmaceutics, vol. 15, no. 2, 567. https://doi.org/10.3390/pharmaceutics15020567

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T1 - Low-Level Laser Treatment Induces the Blood-Brain Barrier Opening and the Brain Drainage System Activation: Delivery of Liposomes into Mouse Glioblastoma

AU - Semyachkina-Glushkovskaya, Oxana

AU - Bragin, Denis

AU - Bragina, Olga

AU - Socolovski, Sergey

AU - Shirokov, Alexander

AU - Fedosov, Ivan

AU - Ageev, Vasily

AU - Blokhina, Inna

AU - Dubrovsky, Alexander

AU - Telnova, Valeria

AU - Terskov, Andrey

AU - Khorovodov, Alexander

AU - Elovenko, Daria

AU - Evsukova, Arina

AU - Zhoy, Maria

AU - Agranovich, Ilana

AU - Vodovozova, Elena

AU - Alekseeva, Anna

AU - Kurths, Jürgen

AU - Rafailov, Edik

N1 - Copyright © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Funding: S.-G.O., I.F., A.S., I.B., A.K., A.T., D.E., V.A., A.E., M.Z., V.A. and A.D. were supported by Grant from the Russian Ministry of Science and High EducationNo 075-15-2022-1094; A.S. and A.K. were supported by Grant from RSF No 21-75-10088; 23-25-00296. D.B. was supported by NIH R21NS091600 and R01NS112808. E.R. and S.S. gratefully acknowledge funding from EU’s H2020 FET OPEN NEUROPA project under the Grant Agreement No. 863214. E.V. and A.A. were supported by Grant from RSF No 21-74-20177 in part of the synthesis of fluorescently labeled liposomes.

PY - 2023/2/8

Y1 - 2023/2/8

N2 - The progress in brain diseases treatment is limited by the blood-brain barrier (BBB), which prevents delivery of the vast majority of drugs from the blood into the brain. In this study, we discover unknown phenomenon of opening of the BBBB (BBBO) by low-level laser treatment (LLLT, 1268 nm) in the mouse cortex. LLLT-BBBO is accompanied by activation of the brain drainage system contributing effective delivery of liposomes into glioblastoma (GBM). The LLLT induces the generation of singlet oxygen without photosensitizers (PSs) in the blood endothelial cells and astrocytes, which can be a trigger mechanism of BBBO. LLLT-BBBO causes activation of the ABC-transport system with a temporal decrease in the expression of tight junction proteins. The BBB recovery is accompanied by activation of neuronal metabolic activity and stabilization of the BBB permeability. LLLT-BBBO can be used as a new opportunity of interstitial PS-free photodynamic therapy (PDT) for modulation of brain tumor immunity and improvement of immuno-therapy for GBM in infants in whom PDT with PSs, radio- and chemotherapy are strongly limited, as well as in adults with a high allergic reaction to PSs.

AB - The progress in brain diseases treatment is limited by the blood-brain barrier (BBB), which prevents delivery of the vast majority of drugs from the blood into the brain. In this study, we discover unknown phenomenon of opening of the BBBB (BBBO) by low-level laser treatment (LLLT, 1268 nm) in the mouse cortex. LLLT-BBBO is accompanied by activation of the brain drainage system contributing effective delivery of liposomes into glioblastoma (GBM). The LLLT induces the generation of singlet oxygen without photosensitizers (PSs) in the blood endothelial cells and astrocytes, which can be a trigger mechanism of BBBO. LLLT-BBBO causes activation of the ABC-transport system with a temporal decrease in the expression of tight junction proteins. The BBB recovery is accompanied by activation of neuronal metabolic activity and stabilization of the BBB permeability. LLLT-BBBO can be used as a new opportunity of interstitial PS-free photodynamic therapy (PDT) for modulation of brain tumor immunity and improvement of immuno-therapy for GBM in infants in whom PDT with PSs, radio- and chemotherapy are strongly limited, as well as in adults with a high allergic reaction to PSs.

KW - blood-brain barrier

KW - brain drainage system

KW - glioblastoma

KW - infrared low-intensity laser treatment

KW - liposomes

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U2 - 10.3390/pharmaceutics15020567

DO - 10.3390/pharmaceutics15020567

M3 - Article

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JO - Pharmaceutics

JF - Pharmaceutics

IS - 2

M1 - 567

ER -

Low-Level Laser Treatment Induces the Blood-Brain Barrier Opening and the Brain Drainage System Activation: Delivery of Liposomes into Mouse Glioblastoma

Abstract

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Keywords

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