Empowered in-vivo functional brain imaging with Ferucarbotran-loaded red blood cells

Our previous MPI data validated that engineered SPIO-loaded RBCs have improved in-vivo stability over the corresponding free SPIO-based contrast agents. We now demonstrate the efficiency of these biomimetic constructs in the field of functional brain imaging using Functional Magnetic Resonance Imaging (fMRI). Data was obtained in an anesthetised rodent model using a 7 Tesla preclinical MRI system (Bruker, Biospec 70/30). Responses to i) neuronal activation of the somatosensory barrel cortex (via repeated electrical stimulation of the whisker pad) and ii) respiratory challenge (10% increased FiCO2) were recorded pre and post injection of 1.5 ml of human Ferucarbotran-loaded-RBCs (corresponding to 16 µmoles Fe) as an intravenous SPIO-based tracer. Post injection we found high contrast-to-noise, Cerebral Blood Volume (CBV) weighted signal changes in line with previous preclinical fMRI studies using free SPIO nanoparticles. CBV-fMRI offers functional sensitivity at cortical laminar resolutions as a significant advantage over routine Blood Oxygenation Level Dependent (BOLD) fMRI. Furthermore, RBCs are biocompatible and biodegradable iron oxide-carriers. Hence, our novel approach permits the easier targeting of CBV markers with higher contrast (over BOLD fMRI) and in the future could drive development of longitudinal assessment of brain function using safe and long half-life SPIO-based tracers

Encapsulation in human and murine erythrocytes of the Synomag®-D-PEG-OMe tracer for MPI application

Recently, the potential of red blood cells (RBCs) loaded with superparamagnetic iron oxide (SPIO)-based nanoparticles as new blood-pool tracer material for the Magnetic Particle Imaging (MPI) has been investigated. It was shown that the encapsulation of SPIO-based contrast agents in the RBCs increase the circulation time in blood of these nanomaterials. However, not all iron oxide nanoparticles are eligible to the encapsulation into RBCs, depending on several factors such as dispersant agent nature, nanoparticle size and synthesis protocol. Therefore, we have recently started a program to identify those nanoparticles that can be potentially loaded with our method into RBCs. The goal is to produce biocompatible SPIO-RBCs carriers that can be used as new intravascular magnetic susceptible agents in biomedical applications, such as MRI and MPI. Here, we report the in vitro results obtained by using the Synomag®-D-PEG-OMe nanoparticle suspension (micromod Partikeltechnologie GmbH) with both human and murine red blood cells. MPS analysis showed that human Synomag®-D-PEG-OMe-loaded RBCs produced a signal that is weaker respect to the remarkable signal of ferucarbotran loaded-RBCs prepared at the same condition, but it is to be noted that the encapsulation efficiency of Synomag®-D-PEG-OMe into cells is lower compared to ferucarbotran nanoparticles

Compatibility of Nucleobases Containing Pt(II) Complexes with Red Blood Cells for Possible Drug Delivery Applications

The therapeutic advantages of some platinum complexes as major anticancer chemotherapeutic agents and of nucleoside analogue-based compounds as essential antiviral/antitumor drugs are widely recognized. Red blood cells (RBCs) offer a potential new strategy for the targeted release of therapeutic agents due to their biocompatibility, which can protect loaded drugs from inactivation in the blood, thus improving biodistribution. In this study, we evaluated the feasibility of loading model nucleobase-containing Pt(II) complexes into human RBCs that were highly stabilized by four N-donors and susceptible to further modification for possible antitumor/antiviral applications. Specifically, platinum-based nucleoside derivatives [PtII(dien)(N7-Guo)]2+, [PtII(dien)(N7-dGuo)]2+, and [PtII(dien)(N7-dGTP)] (dien = diethylenetriamine; Guo = guanosine; dGuo = 20-deoxy-guanosine; dGTP = 50-(20-deoxy)-guanosine-triphosphate) were investigated. These Pt(II) complexes were demonstrated to be stable species suitable for incorporation into RBCs. This result opens avenues for the possible incorporation of other metalated nucleobases analogues, with potential antitumor and/or antiviral activity, into RBCs