Development of MR Contrast Agents Facilitating the Tracking of Islet Transplantation and to Reduce

In vivo imaging, being non-invasive, quantitative, and repetitive, of targeted macromolecules and biological processes have recently attracted widespread interests. However, most of the current techniques lack the resolution to study events unless with the use of high-contrast materials or tissue-specific luminescence. Besides Gadolinium (Gd), which was the most common contrast agent, the use of superparamagnetic iron oxide (SPIO) nanoparticles leads to the combination of high spatial resolution of magnetic resonance (MR) imaging and the high specificity of magnetic markers. Our recent studies have developed an in situ coating method for preparing SPIO coated with γ-ray irradiated chitosan and demonstrated its potential as a great MR T2 contrast agent for grafted islet tracking. Due to the unique transfection feature of chitosan, we intend to again develop such contrast agents, equipping them with immunosuppressive characteristics, and apply in islet grafting. The therapeutic gene vectors which encode molecules including interleulin-10 (IL-10), cytotoxic T-lymphocyte antigen 4 (CTLA-4), and/or program death 1 ligand 1 (PD-L1) will be complexed with the chitosan coating for encapsulating SPIO. The as prepared contrast agents (chitosan-plasmid DNA complexes encapsulating SPIO) with immunosuppressive ability will be evaluated for their beneficial effects on islet allo-grafting both in normal and/or autoimmune on-obese diabetic (NOD) mice. The specific aims include: 1. Preparation and biophysicochemical characterization of chitosan-plasmid DNA complexes encapsulating SPIO. 2. Determination of the transfection efficacy of chitosan-plasmid DNA complexes encapsulating SPIO in vitro. 3. Evaluation of the beneficial effects of chitosan-plasmid DNA complexes encapsulating SPIO on islet iso- and allo-grafting in vivo. 4. Identification of the effects of chitosan-plasmid DNA complexes encapsulating SPIO on autoimmune responses in NOD mice. In summary, this 4-year proposal aims to equip the current MR contrast agent SPIO with immune-modulatory function, and such intention would not only benefit for grafted islet tracking but also reducing the incompatible immune responses leading to the graft rejection or damage. To our knowledge, it is a novel invention.

Project ID:PC10108-0810
External Project ID:NSC101-2320-B182-027-MY3