Iron-based compounds coordinated with phospho-polymers as biocompatible probes for dual 31P/1H magnetic resonance imaging and spectroscopy.

In this work, we present the synthesis and evaluation of magnetic resonance (MR) properties of novel phosphorus/iron-containing probes for dual 31P and 1H MR imaging and spectroscopy (MRI and MRS). The presented probes are composed of biocompatible semitelechelic and multivalent phospho-polymers based on poly(2-methacryloyloxyethyl phosphorylcholine) (pMPC) coordinated with small paramagnetic Fe3+ ions or superparamagnetic maghemite (γ-Fe2O3) nanoparticles via deferoxamine group linked to the end or along the polymer chains. All probes provided very short 1H T1 and T2 relaxation times even at low iron concentrations. The presence of iron had a significant impact on the shortening of 31P relaxation, with the effect being more pronounced for probes based on γ-Fe2O3 and multivalent polymer. While the water-soluble probe having one Fe3+ ion per polymer chain was satisfactorily visualized by both 31P-MRS and 31P-MRI, the probe with multiple Fe3+ ions could only be detected by 31P-MRS, and the probes consisting of γ-Fe2O3 nanoparticles could not be imaged by either technique due to their ultra-short 31P relaxations. In this proof-of-principle study performed on phantoms at a clinically relevant magnetic fields, we demonstrated how the different forms and concentrations of iron affect both the 1H MR signal of the surrounding water molecules and the 31P MR signal of the phospho-polymer probe. Thus, this double contrast can be exploited to simultaneously visualize body anatomy and monitor probe biodistribution.

Phosphorus-Containing Polymers as Sensitive Biocompatible Probes for 31P Magnetic Resonance.

The visualization of organs and tissues using 31P magnetic resonance (MR) imaging represents an immense challenge. This is largely due to the lack of sensitive biocompatible probes required to deliver a high-intensity MR signal that can be distinguished from the natural biological background. Synthetic water-soluble phosphorus-containing polymers appear to be suitable materials for this purpose due to their adjustable chain architecture, low toxicity, and favorable pharmacokinetics. In this work, we carried out a controlled synthesis, and compared the MR properties, of several probes consisting of highly hydrophilic phosphopolymers differing in composition, structure, and molecular weight. Based on our phantom experiments, all probes with a molecular weight of ~3-400 kg·mol-1, including linear polymers based on poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), poly(ethyl ethylenephosphate) (PEEP), and poly[bis(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)]phosphazene (PMEEEP) as well as star-shaped copolymers composed of PMPC arms grafted onto poly(amidoamine) dendrimer (PAMAM-g-PMPC) or cyclotriphosphazene-derived cores (CTP-g-PMPC), were readily detected using a 4.7 T MR scanner. The highest signal-to-noise ratio was achieved by the linear polymers PMPC (210) and PMEEEP (62) followed by the star polymers CTP-g-PMPC (56) and PAMAM-g-PMPC (44). The 31P T1 and T2 relaxation times for these phosphopolymers were also favorable, ranging between 1078 and 2368 and 30 and 171 ms, respectively. We contend that select phosphopolymers are suitable for use as sensitive 31P MR probes for biomedical applications.

Decellularized Pancreatic Tail as Matrix for Pancreatic Islet Transplantation into the Greater Omentum in Rats.

Infusing pancreatic islets into the portal vein currently represents the preferred approach for islet transplantation, despite considerable loss of islet mass almost immediately after implantation. Therefore, approaches that obviate direct intravascular placement are urgently needed. A promising candidate for extrahepatic placement is the omentum. We aimed to develop an extracellular matrix skeleton from the native pancreas that could provide a microenvironment for islet survival in an omental flap. To that end, we compared different decellularization approaches, including perfusion through the pancreatic duct, gastric artery, portal vein, and a novel method through the splenic vein. Decellularized skeletons were compared for size, residual DNA content, protein composition, histology, electron microscopy, and MR imaging after repopulation with isolated islets. Compared to the other approaches, pancreatic perfusion via the splenic vein provided smaller extracellular matrix skeletons, which facilitated transplantation into the omentum, without compromising other requirements, such as the complete depletion of cellular components and the preservation of pancreatic extracellular proteins. Repeated MR imaging of iron-oxide-labeled pancreatic islets showed that islets maintained their position in vivo for 49 days. Advanced environmental scanning electron microscopy demonstrated that islets remained integrated with the pancreatic skeleton. This novel approach represents a proof-of-concept for long-term transplantation experiments.

Phosphorus-Containing Polymeric Zwitterion: A Pioneering Bioresponsive Probe for 31 P-Magnetic Resonance Imaging.

31 P-magnetic resonance (MR) is an important diagnostic technique currently used for tissue metabolites assessing, but it also has great potential for visualizing the internal body structures. However, due to the low physiological level of phosphorus-containing biomolecules, precise imaging requires the administration of an exogenous probe. Herein, this work describes the synthesis and MR characterization of a pioneering metal-free 31 P-MR probe based on phosphorus-containing polymeric zwitterion. The developed probe (pTMPC) is a well-defined water-soluble macromolecule characterized by a high content of naturally rare phosphorothioate groups providing a high-intensity 31 P-MR signal clearly distinguishable from biological background both in vitro and in vitro. In addition, pTMPC can serve as a sensitive 31 P-MR sensor of pathological conditions in vivo because it undergoes oxidation-induced structural changes in the presence of reactive oxygen species (ROS). Add to this the favorable 1 H and 31 P T1 /T2 relaxation times and biocompatibility, pTMPC represents a conceptually new diagnostic, whose discovery opens up new possibilities in the field of 31 P-MR spectroscopy and imaging.