The 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.

The novel fluorescent membrane probe, bis(cyclohexyl)-BODIPY (BCHB)-labeled phosphatidylcholine, is structurally similar to 1,3,5,7-tetramethyl-BODIPY (TMB)-labeled phosphatidylcholine. Formally, BCHB and TMB have similar systems of conjugated bonds; however, spectral properties of the probes are notably different. BCHB and TMB have a perfect spectral overlap. The fact makes BCHB a good FRET acceptor for TMB. Thus, the pair of phosphatidylcholines labeled with BCHB and TMB is a good tool for FRET-based membrane studies, e.g. lipid transfer studies.