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

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.

Publication DOI: https://doi.org/10.3390/pharmaceutics15020567
Divisions: College of Engineering & Physical Sciences > Aston Institute of Photonics Technology (AIPT)
College of Engineering & Physical Sciences
Additional Information: 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.
Uncontrolled Keywords: blood-brain barrier,brain drainage system,glioblastoma,infrared low-intensity laser treatment,liposomes,Pharmaceutical Science
Publication ISSN: 1999-4923
Last Modified: 23 May 2024 07:20
Date Deposited: 17 Feb 2023 08:56
Full Text Link:
Related URLs: https://www.mdp ... 9-4923/15/2/567 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2023-02-08
Published Online Date: 2023-02-08
Accepted Date: 2023-02-02
Authors: Semyachkina-Glushkovskaya, Oxana
Bragin, Denis
Bragina, Olga
Socolovski, Sergey (ORCID Profile 0000-0001-7445-7204)
Shirokov, Alexander
Fedosov, Ivan
Ageev, Vasily
Blokhina, Inna
Dubrovsky, Alexander
Telnova, Valeria
Terskov, Andrey
Khorovodov, Alexander
Elovenko, Daria
Evsukova, Arina
Zhoy, Maria
Agranovich, Ilana
Vodovozova, Elena
Alekseeva, Anna
Kurths, Jürgen
Rafailov, Edik (ORCID Profile 0000-0002-4152-0120)

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