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- ItemPhotobiomodulation of lymphatic drainage and clearance: Perspective strategy for augmentation of meningeal lymphatic functions(Washington, DC : Optica, 2020) Semyachkina-Glushkovskaya, Oxana; Abdurashitov, Arkady; Dubrovsky, Alexander; Klimova, Maria; Agranovich, Ilana; Terskov, Andrey; Shirokov, Alexander; Vinnik, Valeria; Kuzmina, Anna; Lezhnev, Nikita; Blokhina, Inna; Shnitenkova, Anastassia; Tuchin, Valery; Rafailov, Edik; Kurths, JurgenThere is a hypothesis that augmentation of the drainage and clearing function of the meningeal lymphatic vessels (MLVs) might be a promising therapeutic target for preventing neurological diseases. Here we investigate mechanisms of photobiomodulation (PBM, 1267 nm) of lymphatic drainage and clearance. Our results obtained at optical coherence tomography (OCT) give strong evidence that low PBM doses (5 and 10 J/cm2) stimulate drainage function of the lymphatic vessels via vasodilation (OCT data on the mesenteric lymphatics) and stimulation of lymphatic clearance (OCT data on clearance of gold nanorods from the brain) that was supported by confocal imaging of clearance of FITC-dextran from the cortex via MLVs. We assume that PBM-mediated relaxation of the lymphatic vessels can be possible mechanisms underlying increasing the permeability of the lymphatic endothelium that allows molecules transported by the lymphatic vessels and explain PBM stimulation of lymphatic drainage and clearance. These findings open new strategies for the stimulation of MLVs functions and non-pharmacological therapy of brain diseases.
- ItemIntranasal Delivery of Liposomes to Glioblastoma by Photostimulation of the Lymphatic System(Basel : MDPI, 2022) Semyachkina-Glushkovskaya, Oxana; Shirokov, Alexander; Blokhina, Inna; Telnova, Valeria; Vodovozova, Elena; Alekseeva, Anna; Boldyrev, Ivan; Fedosov, Ivan; Dubrovsky, Alexander; Khorovodov, Alexandr; Terskov, Andrey; Evsukova, Arina; Elovenko, Daria; Adushkina, Viktoria; Tzoy, Maria; Agranovich, Ilana; Kurths, Jürgen; Rafailov, EdikThe blood–brain barrier (BBB) limits the delivery of majority of cancer drugs and thereby complicates brain tumor treatment. The nasal-brain-lymphatic system is discussed as a pathway for brain drug delivery overcoming the BBB. However, in most cases, this method is not sufficient to achieve a therapeutic effect due to brain drug delivery in a short distance. Therefore, it is necessary to develop technologies to overcome the obstacles facing nose-to-brain delivery of promising pharmaceuticals. In this study, we clearly demonstrate intranasal delivery of liposomes to the mouse brain reaching glioblastoma (GBM). In the experiments with ablation of the meningeal lymphatic network, we report an important role of meningeal pathway for intranasal delivery of liposomes to the brain. Our data revealed that GBM is characterized by a dramatic reduction of intranasal delivery of liposomes to the brain that was significantly improved by near-infrared (1267 nm) photostimulation of the lymphatic vessels in the area of the cribriform plate and the meninges. These results open new perspectives for non-invasive improvement of efficiency of intranasal delivery of cancer drugs to the brain tissues using nanocarriers and near-infrared laser-based therapeutic devices, which are commercially available and widely used in clinical practice.