Iron (III)-Quercetin Complex: Synthesis, Physicochemical Characterization, and MRI Cell Tracking toward Potential Applications in Regenerative Medicine

Abstract

In cell therapy, contrast agents T1 and T2 are both needed for the labeling and tracking of transplanted stem cells over extended periods of time through magnetic resonance imaging (MRI). Importantly, the metal-quercetin complex via coordination chemistry has been studied extensively for biomedical applications, such as anticancer therapies and imaging probes. Herein, we report on the synthesis, characterization, and labeling of the iron (III)-quercetin complex, “IronQ,” in circulating proangiogenic cells (CACs) and also explore tracking via the use of a clinical 1.5 Tesla (T) MRI scanner. Moreover, IronQ had a paramagnetic T1 positive contrast agent property with a saturation magnetization of 0.155 emu/g at 1.0 T and longitudinal relaxivity (r1) values of 2.29 and 3.70 mM−1s−1 at 1.5 T for water and human plasma, respectively. Surprisingly, IronQ was able to promote CAC growth in conventional cell culture systems without the addition of specific growth factors. Increasing dosages of IronQ from 0 to 200 μg/mL led to higher CAC uptake, and maximum labeling time was achieved in 10 days. The accumulated IronQ in CACs was measured by two methodologies, an inductively coupled plasma optical emission spectrometry (ICP-EOS) and T1-weighted MRI. In our research, we confirmed that IronQ has excellent dual functions with the use of an imaging probe for MRI. IronQ can also act as a stimulating agent by favoring circulating proangiogenic cell differentiation. Optimistically, IronQ is considered beneficial for alternative labeling and in the tracking of circulation proangiogenic cells and/or other stem cells in applications of cell therapy through noninvasive magnetic resonance imaging in both preclinical and clinical settings.

Iron-Quercetin Complex Preconditioning Human Peripheral Blood Mononuclear Cells Accelerates Angiogenic and Wound Healing Efficacy

“…It has been shown that IronQ can act as a stimulating agent by favoring the proangiogenic cell differentiation of PBMCs. Moreover, IronQ is highly sensitive and has no toxicity but enhanced the therapeutic e ciency of labeled cells [29]. These results are suggesting that IronQ exerts the most outstanding excellent dual functions in applications of cell-based therapy.…”

“…PBMCs cultured under IronQ complex results in accelerating proliferative of adherent spindle-shaped cells and number of early outgrowth colonies (CFU-Hill) Firstly, the appropriate concentration of the Iron-Quercetin complex (IronQ) was determined by cytotoxicity assay in a previous study [29]. We found that 125 µg/mL of IronQ complex is not toxic to peripheral blood mononuclear cells (PBMCs) when cultured for a long time (i.e., for one month).…”

“…IronQ modulated the cellular characteristic of PBMCs to enrich contained blood-derived spindle-shape-like cells (EPCs) during in vitro expansion. Simultaneously, there is the potential to visualize IronQ labeled cells transplant with MR imaging via the paramagnetic properties of IronQ [29]. The Iron-Quercetin complex has some practical advantages over other types of MRI contrast agents when used for clinical purposes.…”

Iron–Quercetin Complex Preconditioning of Human Peripheral Blood Mononuclear Cells Accelerates Angiogenic and Fibroblast Migration: Implications for Wound Healing

“…Firstly, the appropriate concentration of the iron-quercetin complex (IronQ) was determined by cytotoxicity assay in a previous study [33]. We found that 125 µg/mL of IronQ complex was not toxic to peripheral blood mononuclear cells (PBMCs) when cultured for a long time (i.e., for one month).…”

“…IronQ modulates the cellular characteristics of PBMCs to enrich the blood-derived spindle-shape-like cells (EPCs) during in vitro expansion. Simultaneously, there is the potential to visualize IronQ-labeled cells that have been transplanted with MR imaging via the paramagnetic properties of IronQ [33]. The iron-quercetin complex has some practical advantages over other types of MRI contrast agents when used for clinical purposes.…”