Department of Immunology and Oncology, and NanoBiomedicine Initiative, Centro Nacional de Biotecnología (CNB)-CSIC, Darwin 3, Cantoblanco, 28049, Madrid, Spain.
Animal Health Research Centre (CISA)-INIA, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Valdeolmos, 28130, Madrid, Spain.
J Nanobiotechnology. 2019 Jan 22;17(1):14. doi: 10.1186/s12951-019-0440-z.
BACKGROUND: T lymphocytes are highly dynamic elements of the immune system with a tightly regulated migration. T cell-based transfer therapies are promising therapeutic approaches which in vivo efficacy is often limited by the small proportion of administered cells that reaches the region of interest. Manipulating T cell localisation to improve specific targeting will increase the effectiveness of these therapies. Nanotechnology has been successfully used for localized release of drugs and biomolecules. In particular, magnetic nanoparticles (MNPs) loaded with biomolecules can be specifically targeted to a location by an external magnetic field (EMF). The present work studies whether MNP-loaded T cells could be targeted and retained in vitro and in vivo at a site of interest with an EMF. RESULTS: T cells were unable to internalize the different MNPs used in this study, which remained in close association with the cell membrane. T cells loaded with an appropriate MNP concentration were attracted to an EMF and retained in an in vitro capillary flow-system. MNP-loaded T cells were also magnetically retained in the lymph nodes after adoptive transfer in in vivo models. This enhanced in vivo retention was in part due to the EMF application and to a reduced circulating cell speed within the organ. This combined use of MNPs and EMFs did not alter T cell viability or function. CONCLUSIONS: These studies reveal a promising approach to favour cell retention that could be implemented to improve cell-based therapy.
背景:T 淋巴细胞是免疫系统中具有高度动态性的元素,其迁移受到严格调控。基于 T 细胞的转移治疗是一种很有前途的治疗方法,但在体内的疗效往往受到到达靶区的给药细胞比例小的限制。操纵 T 细胞定位以提高特定靶向性将提高这些疗法的有效性。纳米技术已成功用于药物和生物分子的局部释放。特别是,负载生物分子的磁性纳米颗粒(MNPs)可以通过外部磁场(EMF)被靶向到特定位置。本工作研究了负载 MNPs 的 T 细胞是否可以通过 EMF 在体外和体内的靶部位被靶向和保留。
结果:本研究中使用的不同 MNPs 无法被 T 细胞内化,它们仍然与细胞膜密切相关。负载适当 MNP 浓度的 T 细胞被 EMF 吸引,并在体外毛细管流动系统中被保留。负载 MNPs 的 T 细胞在体内模型中的过继转移后也能在淋巴结中被磁性保留。这种增强的体内保留部分归因于 EMF 的应用和器官内循环细胞速度的降低。这种 MNPs 和 EMFs 的联合使用不会改变 T 细胞的活力或功能。
结论:这些研究揭示了一种有前途的促进细胞保留的方法,可用于改善基于细胞的治疗。
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