Iron(III)–Quercetin Complexes’ Safety for MRI Cell Tracking in Cell Therapy Applications: Cytotoxic and Genotoxic Assessment

Abstract

The theranostic agent iron–quercetin complex (IronQ) provides a T1-positive magnetic resonance imaging (MRI) contrast agent. The magnetically IronQ-labeled cells can be used for cell tracking and have active biological applications in promoting cell and tissue regeneration. However, a detailed investigation of IronQ’s cytotoxicity and genotoxicity is necessary. Thus, this study aimed to evaluate the possibility of IronQ inducing cytotoxicity and genotoxicity in peripheral blood mononuclear cells (PBMCs). We evaluated the vitality of cells, the production of reactive oxygen species (ROS), the level of antioxidant enzymes, and the stability of the genetic material in PBMCs treated with IronQ. The results show that IronQ had a negligible impact on toxicological parameters such as ROS production and lipid peroxidation, indicating that it is not harmful. IronQ-labeled PMBCs experienced an insignificant depletion of antioxidant enzyme levels at the highest concentration of IronQ. There is no evident genotoxicity in the magnetically IronQ-labeled PBMCs. The results show that IronQ does not potentiate the cytotoxicity and genotoxicity effects of the labeled PMBCs and might be safe for therapeutic and cell tracking purposes. These results could provide a reference guideline for the toxicological analysis of IronQ in in vivo studies.

Identifying transcriptomic profiles of iron–quercetin complex treated peripheral blood mononuclear cells from healthy volunteers and diabetic patients

“…IronQ treatment was shown to slightly increase the production of reactive oxygen species (ROS) 18 , thus inducing oxidative stress and cellular activation. Our investigation demonstrated the upregulation of various stress-responsive and detoxifying genes, including MGST1, HPGDS, NQO1, PRDX1, TXN, TXNRD1, and EPX .…”

“…The paramagnetic IronQ has shown significant promise as a versatile theranostic agent, as it is both a contrast agent for magnetic resonance imaging and an invigorating therapeutic agent. This agent has demonstrated safety in cell tracking and therapy 18 . Given that our IronQ-PBMC-derived angiogenic cells originated from a readily accessible source and exhibited renewable tissue properties, as well as their cultivation using a versatile theranostic agent that was capable of stimulating PBMCs and enabling cell tracking via MRI, these cells hold tremendous promise for use in tissue repair strategies.…”

“…This innovative contrast agent (IronQ) has been extensively studied and has shown promising results in various biomedical applications, including cell tracking and active biological interventions for promoting cell and tissue regeneration 17 , 18 , 24 . However, the interactions that affect transcriptome profiles and the underlying molecular mechanisms that enhance the therapeutic properties of PBMCs still need to be fully understood.…”

Mincle as a potential intervention target for the prevention of inflammation and fibrosis (Review)

“…A recently published study by Yang et al ( 99 ) revealed that co-treatment of bone marrow mesenchymal stem cells (BMSCs) with Iron(III)-quercetin complexes (IronQ), which has excellent dual functions with the use of an imaging probe for MRI and act as a stimulating agent by favoring circulating proangiogenic cell differentiation ( 100 – 102 ), alleviates intracerebral hemorrhage (ICH) by ameliorating inflammation-induced neurological deficits through inhibition of the Mincle/Syk signaling pathway. The conditioned medium generated from BMSC combined with IronQ reduced the LPS-induced inflammation, Mincle expression and its downstream target activity in the BV2 cell line.…”

Recent Advances in Nanoformulations for Quercetin Delivery

“…The main nanomaterials used for their fabrication are gold and silver, the oxides of iron, cooper, and the dioxides of titanium and silicon [ 160 ]. The QUE formulation into inorganic NPs is used either for imaging or for therapeutic purposes, especially in the cases of cancers, neurological, or metabolic diseases [ 161 , 162 , 163 , 164 ]. This review mainly focuses on the QUE delivery systems and includes the studies that propose inorganic nano-formulations assessed in-vitro or at preclinical levels in different disease conditions.…”