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
Affiliations
Oxana Semyachkina-Glushkovskaya
Institute of Physics, Humboldt University, Newtonstrasse 15, 12489 Berlin, Germany
Denis Bragin
Lovelace Biomedical Research Institute, Albuquerque, NM 87108, USA
Olga Bragina
Lovelace Biomedical Research Institute, Albuquerque, NM 87108, USA
Sergey Socolovski
Optoelectronics and Biomedical Photonics Group, Aston Institute of Photonic Technologies, Aston University, Birmingham B4 7ET, UK
Alexander Shirokov
Department of Biology, Saratov State University, Astrakhanskaya 82, 410012 Saratov, Russia
Ivan Fedosov
Department of Biology, Saratov State University, Astrakhanskaya 82, 410012 Saratov, Russia
Vasily Ageev
Department of Biology, Saratov State University, Astrakhanskaya 82, 410012 Saratov, Russia
Inna Blokhina
Department of Biology, Saratov State University, Astrakhanskaya 82, 410012 Saratov, Russia
Alexander Dubrovsky
Department of Biology, Saratov State University, Astrakhanskaya 82, 410012 Saratov, Russia
Valeria Telnova
Department of Biology, Saratov State University, Astrakhanskaya 82, 410012 Saratov, Russia
Andrey Terskov
Department of Biology, Saratov State University, Astrakhanskaya 82, 410012 Saratov, Russia
Alexander Khorovodov
Department of Biology, Saratov State University, Astrakhanskaya 82, 410012 Saratov, Russia
Daria Elovenko
Department of Biology, Saratov State University, Astrakhanskaya 82, 410012 Saratov, Russia
Arina Evsukova
Department of Biology, Saratov State University, Astrakhanskaya 82, 410012 Saratov, Russia
Maria Zhoy
Department of Biology, Saratov State University, Astrakhanskaya 82, 410012 Saratov, Russia
Ilana Agranovich
Department of Biology, Saratov State University, Astrakhanskaya 82, 410012 Saratov, Russia
Elena Vodovozova
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 Moscow, Russia
Anna Alekseeva
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, 117997 Moscow, Russia
Jürgen Kurths
Institute of Physics, Humboldt University, Newtonstrasse 15, 12489 Berlin, Germany
Edik Rafailov
Optoelectronics and Biomedical Photonics Group, Aston Institute of Photonic Technologies, Aston University, Birmingham B4 7ET, UK
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.
