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Photodynamic Opening of the Blood–Brain Barrier and the Meningeal Lymphatic System: The New Niche in Immunotherapy for Brain Tumors
Photodynamic therapy (PDT) is a promising add-on therapy to the current standard of care for patients with glioblastoma (GBM). The traditional explanation of the anti-cancer PDT effects involves the PDT-induced generation of a singlet oxygen in the GBM cells, which causes tumor cell death and microvasculature collapse. Recently, new vascular mechanisms of PDT associated with opening of the blood–brain barrier (OBBB) and the activation of functions of the meningeal lymphatic vessels have been discovered. In this review, we highlight the emerging trends and future promises of immunotherapy for brain tumors and discuss PDT-OBBB as a new niche and an important informative platform for the development of innovative pharmacological strategies for the modulation of brain tumor immunity and the improvement of immunotherapy for GBM.
Intranasal Delivery of Liposomes to Glioblastoma by Photostimulation of the Lymphatic System
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.
Small-Signal Stability of Multi-Converter Infeed Power Grids with Symmetry
Traditional power systems have been gradually shifting to power-electronic-based ones, with more power electronic devices (including converters) incorporated recently. Faced with much more complicated dynamics, it is a great challenge to uncover its physical mechanisms for system stability and/or instability (oscillation). In this paper, we first establish a nonlinear model of a multi-converter power system within the DC-link voltage timescale, from the first principle. Then, we obtain a linearized model with the associated characteristic matrix, whose eigenvalues determine the system stability, and finally get independent subsystems by using symmetry approximation conditions under the assumptions that all converters’ parameters and their susceptance to the infinite bus (Bg) are identical. Based on these mathematical analyses, we find that the whole system can be decomposed into several equivalent single-converter systems and its small-signal stability is solely determined by a simple converter system connected to an infinite bus under the same susceptance Bg. These results of large-scale multi-converter analysis help to understand the power-electronic-based power system dynamics, such as renewable energy integration. As well, they are expected to stimulate broad interests among researchers in the fields of network dynamics theory and applications.