Magnetic resonance–guided, real-time targeted delivery and imaging of magnetocapsules immunoprotecting pancreatic islet cells

Abstract

In type I diabetes mellitus, islet transplantation provides a moment-to-moment fine regulation of insulin. Success rates vary widely, however, necessitating suitable methods to monitor islet delivery, engraftment and survival. Here magnetic resonance-trackable magnetocapsules have been used simultaneously to immunoprotect pancreatic beta-cells and to monitor, non-invasively in real-time, hepatic delivery and engraftment by magnetic resonance imaging (MRI). Magnetocapsules were detected as single capsules with an altered magnetic resonance appearance on capsule rupture. Magnetocapsules were functional in vivo because mouse beta-cells restored normal glycemia in streptozotocin-induced diabetic mice and human islets induced sustained C-peptide levels in swine. In this large-animal model, magnetocapsules could be precisely targeted for infusion by using magnetic resonance fluoroscopy, whereas MRI facilitated monitoring of liver engraftment over time. These findings are directly applicable to ongoing improvements in islet cell transplantation for human diabetes, particularly because our magnetocapsules comprise clinically applicable materials.

Fluorocapsules for Improved Function, Immunoprotection, and Visualization of Cellular Therapeutics with MR, US, and CT Imaging

“…This has previously been demonstrated for islets encapsulated in magnetocapsules, where superparamagnetic nanoparticles were used to provide MR visibility ( 17 ). The purpose of our study was to develop novel immunoprotective alginate microcapsule formulations containing PFCs that may improve glucose responsiveness (insulin secretion) and simultaneously enable multimodality imaging.…”

“…PFOB microcapsules could prove an ideal vehicle for targeted delivery of cellular agents, such as was previously demonstrated for superparamagnetic iron oxide-labeled capsules ( 17 ). Furthermore, because microcapsules containing PFCs are detectable at MR imaging, follow-up examinations with 19 F MR imaging may be performed while avoiding radiation exposure.…”

Mechanistic molecular imaging of cardiac cell therapy for ischemic heart disease

“…High concentrations of radiopaque agents can be incorporated into the microcapsule to enable visualization by X-ray fluoroscopic and computerized tomography (CT) imaging (5). Such technique can be used in combination with reporter gene transfection so as to deliver stem cells using conventional X-ray imaging platforms with follow-up examination by PET/CT or SPECT/CT.…”

Protein-assisted self-assembly of multifunctional nanoparticles

“…Magnetic particles (MP) (6) can be also used as efficient labels for MRI diagnostics and can be precisely quantified even inside a living organism by an external induction probe (7,8). At present, MP are widely studied for hyperthermia of tumors by heating in an AC magnetic field and for targeted delivery of drugs by magnetic field gradients, to avoid systemic intoxication of the organism (9,10). Specific immunological targeting of nanoparticles by antibodies against pathogenic cells is another noteworthy application.…”