Red Blood Cells as Carriers of Iron Oxide-Based Contrast Agents for Diagnostic Applications

Abstract

New biomedical strategies are being developed to improve disease detection, therapeutic monitoring, and treatment efficacy in several contexts for example in anti-angiogenic chemotherapy, and prevention of cardiovascular disorders. The use of contrast agents to improve the sensitivity and resolution of diagnostic imaging modalities, detect lesions or organs, and evaluate organ function was immediately recognized. In the last years, superparamagnetic iron oxide (SPIO) nanoparticles have been clinically used as MRI contrast agents for the diagnosis of liver diseases, due to their ability to shorten T 2 * relaxation times. After the intravenous administration, SPIO nanoparticles are rapidly eliminated from the bloodstream since they are selectively taken up by the Kupffer cells in the liver, spleen, and bone marrow thus improving the clinical tumor detection in these tissues. However, for the investigation of vascular system including functional cardiac diagnosis, angiography and cardiac wall motion assessment, contrast agents with long blood circulation time would be necessary. In fact, imaging applications for long-term monitoring require the repeated administration of SPIO bolus injections, which complicates quantitative comparisons due to the temporal variations in concentration. In this context, researchers have developed several SPIO delivery systems based on red blood cells (RBCs) used as carriers to increase the blood circulation time of contrast agents. Encapsulation of SPIOs into RBCs appears the most attractive strategy to obtain magnetic RBC-constructs suitable for MRI and MPI analyses of blood vascular system.

Reengineering red blood cells for cellular therapeutics and diagnostics

“…RBC can be engineered also for the encapsulation of a large number of nanomaterials useful in diagnostic applications, especially in the visualization of the vascular system by fluorescent techniques or MPI and MRI …”

Soft erythrocyte-based bacterial microswimmers for cargo delivery

“…Moreover, RBCs are uniquely specialized to carry maximum loads by losing their nuclei through maturation, which also allows them to deform and squeeze repeatedly without blocking any capillaries that can be as small as half of their diameter (41)(42)(43). Because of such unique capabilities, RBCs have been used intensively as passive carriers for delivery of drugs targeting several maladiessuch as oncologic, inflammatory, and neurological diseases-and as imaging agents for diagnostic applications (26,44,45).…”

Endoscopic ultrasound guided injection of iron oxide magnetic nanoparticles for liver and pancreas: a feasibility study in pigs.

“…Depending on their purpose they have been injected locally within a region of interest, orally after gavage following the absorption route or intravenously trying to direct them to the tumor. However, these techniques are rather difficult to control as the biological response of the targeted tissue requires a large amount of MNPs to fulfill the therapeutic effect [15]. Generally, vascular injection and distribution of MNPs require their passage through three phases: blood stream clearance, extravasation and interstitial space depositing from where they may attack the cancer cells.…”