D'Elios M M, Aldinucci A, Amoriello R, Benagiano M, Bonechi E, Maggi P, Flori A, Ravagli C, Saer D, Cappiello L, Conti L, Valtancoli B, Bencini A, Menichetti L, Baldi G, Ballerini C
Department of Clinical and Experimental Medicine, University of Florence Italy.
Department of Neuroscience, Psychology, Drug and Child Health, University of Florence Italy
RSC Adv. 2018 Jan 3;8(2):904-913. doi: 10.1039/c7ra11290d. eCollection 2018 Jan 2.
Progress in nanotechnology has determined new strategies concerning drug delivery into the central nervous system for the treatment of degenerative and inflammatory diseases. To date, brain targeting through systemic drug administration, even in a nano-composition, is often unsuccessful. Therefore, we investigated the possibility of loading T lymphocytes with PGLA-PEG COOH magnetite nanoparticles (30 nm), which can be built up to easily bind drugs and monoclonal antibodies, and to exploit the ability of activated T cells to cross the blood-brain barrier and infiltrate the brain parenchyma. Iron oxide nanoparticles have been widely used in biomedical applications due to their theranostic properties and are therefore a well-established nanomaterial. The magnetite core is easily hybridized with polymeric compounds that may enhance the possibility of the nanoparticles entering cells with low phagocytic properties. Taking advantage of these material characteristics, after assessment of the viability and functionality of nano-loaded MOG specific T cells, we transferred cells containing the nano-cargo into naïve mice affected by experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. By means of histological and immunohistological methods, we were able to identify the nano-loaded T cells in the central nervous system. Our data demonstrated that T cells containing nanomaterials hold the possibility of carrying and releasing nanoparticles in the brain.
纳米技术的进步为治疗退行性和炎症性疾病的中枢神经系统药物递送确定了新策略。迄今为止,即使是纳米制剂形式的全身给药脑靶向通常也不成功。因此,我们研究了用PGLA-PEG COOH磁铁矿纳米颗粒(30纳米)装载T淋巴细胞的可能性,这种纳米颗粒可以构建成易于结合药物和单克隆抗体,并利用活化T细胞穿越血脑屏障和浸润脑实质的能力。由于其诊疗特性,氧化铁纳米颗粒已在生物医学应用中广泛使用,因此是一种成熟的纳米材料。磁铁矿核心很容易与聚合物化合物杂交,这可能会增加纳米颗粒进入低吞噬特性细胞的可能性。利用这些材料特性,在评估纳米负载的髓鞘少突胶质细胞糖蛋白特异性T细胞的活力和功能后,我们将含有纳米货物的细胞转移到患有实验性自身免疫性脑脊髓炎(一种多发性硬化症动物模型)的未致敏小鼠体内。通过组织学和免疫组织学方法,我们能够在中枢神经系统中识别出纳米负载的T细胞。我们的数据表明,含有纳米材料的T细胞有可能在脑中携带和释放纳米颗粒。
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