Jiraporn Kantapan

Background: Iron-polyphenol complexes have emerged as promising theranostic platforms by integrating the biological activity of polyphenols with the redox and coordination properties of iron. Their ability to form discrete molecular complexes and metal-phenolic networks (MPNs) provides tunable control over iron stability, redox activity, cargo delivery, and imaging performance. Since cancer cells exhibit altered iron metabolism and increased dependence on iron availability, these systems offer opportunities for exploiting tumor-specific vulnerabilities through ferroptosis, chemodynamic therapy, and multifunctional molecular imaging. Objectives: This review aims to summarize recent advances in iron-polyphenol systems for cancer theranostics, focusing on the relationship between coordination chemistry, therapeutic mechanisms, and imaging applications. Particular emphasis is placed on discrete Fe-polyphenol complexes, metal-phenolic networks, coordination polymers, and iron-containing hybrid nanoplatforms, including their structural characteristics, anticancer mechanisms, imaging capabilities, biological limitations, and translational challenges. Materials and methods: A structured literature search was conducted using PubMed, Scopus, and Web of Science from database inception to August 2026. Studies related to Fe(II)/Fe(III)-polyphenol coordination systems, including polyphenolic ligands such as catechol, tannic acid, gallic acid, quercetin, and related architectures, were evaluated. Eligible studies included original research investigating coordination chemistry, cancer therapy, molecular imaging, biodistribution, pharmacokinetics, safety, or translational aspects. Non-iron metal-polyphenol systems, iron materials lacking polyphenolic coordination, and unrelated applications were excluded. Results: Iron-polyphenol platforms demonstrate diverse anticancer activities through coordination-controlled mechanisms, including ferroptosis induction, Fe-mediated chemodynamic therapy, photothermal therapy, drug delivery, and immune modulation. The therapeutic and imaging behavior of these systems is strongly influenced by ligand identity, Fe oxidation state, coordination stoichiometry, pH responsiveness, and supramolecular architecture. Iron-polyphenol complexes and MPNs also show potential as gadolinium-free MRI contrast agents, photoacoustic imaging platforms, and immune-cell tracking probes. However, clinical translation remains limited by structural heterogeneity, biological barriers such as protein corona formation and reticuloendothelial system uptake, incomplete biodistribution understanding, long-term iron toxicity concerns, and challenges in scalable manufacturing and quality control. Conclusion: Iron-polyphenol complexes represent a versatile class of theranostic materials that bridge natural product chemistry, redox-regulated cancer therapy, and molecular imaging. Their tunable coordination chemistry enables rational development of multifunctional platforms; however, successful clinical translation requires improved structural standardization, reproducible manufacturing, comprehensive safety evaluation, and quality-controlled production strategies. Continued investigation into coordination-structure-function relationships will be essential for advancing iron-polyphenol systems toward clinically relevant precision cancer theranostics.

Dietary restriction (DR) has been extensively investigated for its capacity to extend lifespan and mitigate age-associated pathologies. In the context of ionizing radiation (IR), DR—implemented through caloric reduction, selective nutrient restriction, or fasting-based regimens—has emerged as a significant modulator of both cellular and systemic responses to radiation exposure. Growing evidence suggests that DR influences radiation outcomes in a highly context-dependent manner, exerting either protective or sensitizing effects depending on tissue type, metabolic status, timing of intervention, and radiation conditions. This review synthesizes current knowledge regarding the mechanisms through which DR modulates responses to IR, with particular emphasis on oxidative stress regulation, inflammatory signaling, mitochondrial homeostasis, DNA damage responses, cellular quality-control pathways, and carcinogenic processes. We further discuss how distinct dietary paradigms interact with nutrient-sensing and stress-adaptive networks to influence radiation sensitivity and tissue recovery. Emerging evidence indicates that the timing, intensity, and composition of dietary interventions critically shape tissue responses to IR, underscoring the importance of considering nutritional status in radiation risk assessment and therapeutic planning. By integrating established findings with emerging mechanistic insights, this review highlights the translational potential of DR for improving outcomes in radiation oncology and reducing radiation-induced injury.

Background: Tumor-associated macrophages (TAMs) frequently adopt an M2-like, immunosuppressive state that promotes tumor growth and therapy resistance. Reprogramming TAMs toward a pro-inflammatory M1 phenotype is a promising strategy to remodel the tumor microenvironment (TME) and enhance treatment responses. We evaluated an iron(III)–quercetin complex (IronQ) as a macrophage-directed, magnetic resonance imaging (MRI)-visible theranostic. Methods: IronQ stability was tested in protein-containing media by dynamic light scattering (DLS). Biocompatibility was assessed in fibroblasts (MRC-5), THP-1–derived macrophages, and non-small-cell lung cancer (NSCLC) cell lines (A549, H460). Cellular uptake was examined by Prussian blue staining and in vitro MRI. Reactive oxygen species (ROS; DCFH-DA), ERK/NF-κB activation (Western blot), and polarization markers (flow cytometry, qRT-PCR, ELISA) were quantified after IronQ exposure. Functional anti-tumor effects were evaluated in non-contact Transwell co-cultures and in 3D tri-culture spheroids (tumor cells, fibroblasts, macrophages). For imaging, agar-embedded spheroids containing IronQ-labeled macrophages were scanned by T1-weighted MRI. Results: IronQ was colloidally stable and well tolerated across cell types within a broad non-toxic window. It accumulated preferentially in macrophages. At low doses, IronQ increased intracellular ROS, activated ERK/NF-κB signaling, upregulated M1 markers ( CD86 , NOS2 , TNFA , IL1B ), and downregulated M2 markers ( CD206 , TGFB1 , IL10 , CCL18 ); these effects attenuated at higher doses, indicating a biphasic response. Functionally, IronQ repolarized IL-4–primed M2 macrophages and indirectly reduced tumor viability in Transwell assays. In 3D spheroids, IronQ limited growth and shifted the secretome toward higher TNF-α and lower IL-10, with IL-6 unchanged. As an imaging agent, IronQ produced dose-dependent T1 hyperintensity in labeled cells and yielded positive T1 signal in spheroids containing IronQ-labeled macrophages. Conclusions: IronQ integrates macrophage-selective uptake, actionable M1 repolarization within a defined dose window, and positive-contrast MRI visibility. These properties support its development as a cost-efficient, multifunctional platform for TAM-focused cancer immunotherapy and image-guided response monitoring.

High-fat diets (HFDs) have become increasingly prevalent in modern societies, driving rising rates of obesity and metabolic syndrome. Concurrently, radiation exposure from medical treatments and environmental sources poses health risks shaped by both biological and environmental factors. This review explores the intersection between HFDs and radiation sensitivity/susceptibility, focusing on how diet-induced metabolic alterations influence the body’s response to radiation. Evidence from preclinical and clinical studies indicates that HFDs significantly alter metabolism, leading to increased oxidative stress and immune system dysregulation. These metabolic changes can exacerbate radiation-induced oxidative stress, inflammation, and DNA damage, potentially increasing radiation sensitivity in normal tissues. Conversely, obesity and HFD-induced metabolic disruptions may activate cellular pathways involved in DNA repair, cell survival, and inflammatory responses, fostering tumor resistance and modifying the tumor microenvironment, which may impair the efficacy of radiation therapy in cancer treatment. Understanding the interplay between diet and radiation exposure is critical for optimizing public health guidelines and improving therapeutic outcomes. These findings underscore the need for further research into dietary interventions that may mitigate radiation-associated risks.

Background: The iron(III)–quercetin complex, known as “IronQ”, is an innovative MRI contrast agent composed of one Fe(III) ion and two quercetin molecules. IronQ is efficiently internalized by cells, enabling T1-weighted MRI tracking. It has demonstrated therapeutic benefits in reducing inflammation in an intracerebral hemorrhage (ICH) mouse model and offers a safer alternative to gadolinium-based agents by avoiding cytotoxicity and genotoxicity. These properties make IronQ a promising candidate for safe and effective MRI contrast enhancement. Purpose: This study aims to further the development of IronQ as an MRI contrast agent by investigating its biodistribution, pharmacokinetics, and acute toxicity in a preclinical animal model. Methods: The relaxivity of IronQ was measured in water and whole blood phantoms. Acute toxicity was evaluated in Sprague Dawley rats administered single intraperitoneal doses of IronQ (75, 150, and 225 μmol Fe/kg BW) over a 14-day period. Pharmacokinetic studies were performed at a dose of 150 μmol Fe/kg BW, with blood iron content analyzed using ICP-OES. For in vivo biodistribution, SD rats were administered an intravenous dose of IronQ (225 μmol Fe/kg BW), followed by MR imaging using a 1.5 T scanner and subsequent tissue-ICP analysis. Results: The longitudinal relaxivity (r₁) of IronQ was measured to be 2.17 mm⁻¹s⁻¹ in ultrapure water and 3.56 mm⁻¹s⁻¹ in whole blood. Acute toxicity studies showed no mortality, morbidity, or significant biochemical changes, with histopathology confirming no irreversible organ damage. Pharmacokinetics revealed peak blood iron content at 1.1 hours post-administration and clearance within 24 hours. MRI demonstrated enhanced T1 signal intensity, particularly in the liver and kidney. Conclusion: These findings provide valuable insights into the safety, pharmacokinetics, and imaging efficacy of IronQ, highlighting its potential as a robust and biocompatible MRI contrast agent.