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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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.
- blood-brain barrier
- brain drainage system
- infrared low-intensity laser treatment