The natural bioactive or nutraceuticals exhibit several health benefits, including anti-inflammatory, anti-cancer, metal chelation, antiviral, and antimicrobial activity. The inherent limitation of nutraceuticals or bioactive ligand(s) in terms of poor pharmacokinetic and other physicochemical properties affects their overall therapeutic efficiency. The excess of iron in the physiological compartments and its varying dynamic oxidation state [Fe(II) and Fe(III)] precipitates various clinical conditions such as non-transferrin bound iron (NTBI), labile iron pool (LIP), ferroptosis, cancer, etc. Though several natural bioactive ligands are proposed to chelate iron, the efficiency of bioactive ligands is limited due to poor bioavailability, denticity, and other related physicochemical properties. The present review provides insight into the relevance of studying the dynamic oxidation state of iron(II) and iron(III) in the physiological compartments and its clinical significance for selecting diagnostics and therapeutic regimes. We suggested a three-pronged approach, i.e., diagnosis, selection of therapeutic regime (natural bioactive), and integration of novel drug delivery systems (NDDS) or nanotechnology-based principles. This systematic approach improves the overall therapeutic efficiency of natural iron chelators to manage iron overload-related clinical conditions.
Keywords: Natural bioactive; cancer; iron; labile iron pool; nanotechnology; non-transferrin bound iron; novel drug delivery system.