Journal
BIOMATERIALS
Volume 30, Issue 10, Pages 1962-1970Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2008.12.043
Keywords
Immunosuppression; Targeted gene delivery; T cell anergy; Nonviral vector; Magnetic resonance imaging
Funding
- Natural Science Foundation of China [20474076, 30571769, 20728403, 50673103]
- Natural Science Foundation of Guangdong Province [7003703]
- Postdoctoral Foundation of China [20070410250]
- Ph.D. Programs Foundation of Ministry of Education of China [20060558083]
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Gene therapy mediated by nonviral vectors provides great advantages over conventional drug therapy in inducing immunosuppression after organ transplantation, yet it was rarely reported because T cells are normally difficult to transfect. In this paper, a nonviral vector that effectively transports genes into T cells is developed by attaching a T cell specific ligand, the CD3 single chain antibody (scAb(CD3)), to the distal ends of poly(ethylene glycol)-grafted polyethylenimine (scAb(CD3)-PEG-g-PEI). This polymer was first complexed with superparamagnetic iron oxide nanoparticles (SPIONs) and was then used to condense plasmid DNA into nanoparticles with an ideally small size and low cytotoxicity. Based on a reporter gene assay, targeting ligand functionalization of the delivery agent leads to 16 fold of enhancement in the gene transfection level in HB8521 cells, a rat T lymphocyte line. This targeting event in cell culture was successfully imaged by MRI scan. Inspiringly, delivery of a therapeutic gene DGK alpha with our MRI-visible delivery agent was likewise efficient, resulting in a 43% inhibition in the stimulated proliferation of HB8521 cells as well as a 38% inhibition in the expression of a major functional cytokine interleukin-2 (IL-2), indicating the effective T cell anergy induced by gene therapy. (C) 2009 Elsevier Ltd. All rights reserved.
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