Abstract
BackgroundT 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.ResultsT 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.ConclusionsThese studies reveal a promising approach to favour cell retention that could be implemented to improve cell-based therapy.
Highlights
T lymphocytes are highly dynamic elements of the immune system with a tightly regulated migration
We successfully show that the use of magnetic nanoparticles (MNPs) and external magnetic field (EMF) can guide and retain T lymphocytes to a target region of interest without critically affecting crucial biological aspects of these cells
We demonstrate that MNP-loaded murine T cells can be magnetically retained in the lymph nodes (LNs), which could be useful to modulate immune response in a pathological context
Summary
T lymphocytes are highly dynamic elements of the immune system with a tightly regulated migration. One promising active approach is based on superparamagnetic iron oxide nanoparticles, which can be localized precisely in the desired area by applying an external magnetic field (EMF) [11]. This approach could promote specific cell accumulation and thereby improve the efficacy of cell transfer therapies. Non-lymphoid cells loaded with these magnetic nanoparticles (MNPs) can be inoculated systemically and attracted to a target tissue in mice by the application of an EMF [12,13,14,15,16,17] These studies focused mainly on enriching stem cells, mesenchymal cells, macrophages or dendritic cells to control tissue injury and immune disorders. The manipulation of highly motile effector lymphoid cells such as T or natural killer (NK) cells to target and accumulate them to a specific region such as lymph nodes (LNs) or solid tumours could be a promising approach to enhance their activity in the desired area
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
