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T-Cell Surface Modification with Synthetic Nanomaterials for Cell-Mediated Delivery to The Central Nervous System

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The future of medicine lies in therapeutic approaches that can be localized to specifically targeted sites of the disease to achieve effective and precise effects. Cell-mediated delivery, especially using cells of the circulatory repertoire such as T lymphocytes, is an attractive opportunity. This study demonstrates the feasibility of T cell carriers to transport model nanoparticles to the central nervous system. This is a very exciting and rapidly evolving area of research with great clinical potential. The use of non-phagocytic cells as carriers (such as T lymphocytes) to transport nanomaterials mainly depends on the attachment of therapeutic carriers to the surface of nanomaterials.

(Bio)chemical tools mainly include non-covalent approaches and covalent approach, are available to modify cell surfaces with synthetic materials. These methods have been used to attach a variety of synthetic materials such as polymer micron-size patches, polymer nano- and microparticles as well as lipid-based nanomaterials. The therapeutic application of surface-modified cells can be used to enhance systemic circulation time of nanoparticles or to mediate the transport of nanomaterials to disease sites or to combine with cell therapy, which has attracted wide attention. There are some important challenges to cell surface modification with synthetic nanoparticles and particles: (i) whether the cellular function remains intact after modification and (ii) whether the nano- or microcarriers remains attached to the cell surface in the systemic circulation upon exposure to shear forces, cell-cell and cell-wall interaction or during endothelial diapedesis. However, the development of novel and exquisite cell surface conjugation methods may help to solve these challenges.

Previous researches have demonstrated that nanoparticles are used to enhance drug delivery across the BBB in an excellent way. Also, nanoparticle carriers facilitate access to the central nervous system in several ways: (i) By opening tight junctions or inducing local toxic effects, resulting in local permeabilization of BBB; (ii) By transcytosis of nanoparticles on BBB; (iii) By endocytosis followed by intracellular release and endocytosis of their payloads; and (iv) By a combination through these pathways. Studies have shown that T cell-mediated polymer nanoparticles use CD4TEM cells as mediators to cross the blood-brain barrier (BBB) to achieve cross-blood-brain barrier delivery. More specifically, CD4TEM cells may be highly attractive carriers that mediate the transport of nanoparticles across BBB for two main reasons. First, the initial organ-targeted nanoparticle enrichment due to brain-seeking T cell migration across brain microvessels; Second, active transport of nanoparticles across the BBB during T-cell diapedesis. Hence, the use of cell carriers for nanoparticle transport represents an innovative step in drug delivery development to the CNS and has been applied to complete BBB models. Compared with the traditional nanoparticle delivery method, this cell-based method has great potential to uptake nanoparticles in CNS.

Cell-mediated drug delivery has immense potential and may contribute to the improvement of targeted therapy in the future, for example in cancer therapy, where T cell therapy has attracted great interest as its potential possibility of combined use of therapeutic nanomaterials in cell-mediated delivery. In principle, modification of cell surface with synthetic nanomaterials apply to a large variety of CNS disorders. It can be used for diagnosis as well as for treatment or in combination with other treatments (e.g., radiotherapy) that cause localized inflammation and which could promote the migration of T cell carriers in these regions.

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