With their distinctive physicochemical features, nanoparticles have gained recognition as effective multifunctional tools for biomedical applications, with designs and compositions tailored for specific uses. Notably, magnetic nanoparticles stand out as first-in-class examples of multiple modalities provided by the iron-based composition. They have long been exploited as contrast agents for magnetic resonance imaging (MRI) or as anti-cancer agents generating therapeutic hyperthermia through high-frequency magnetic field application, known as magnetic hyperthermia (MHT). This review focuses on two more recent applications in oncology using iron-based nanomaterials: photothermal therapy (PTT) and ferroptosis. In PTT, the iron oxide core responds to a near-infrared (NIR) excitation and generates heat in its surrounding area, rivaling the efficiency of plasmonic gold-standard nanoparticles. This opens up the possibility of a dual MHT + PTT approach using a single nanomaterial. Moreover, the iron composition of magnetic nanoparticles can be harnessed as a chemotherapeutic asset. Degradation in the intracellular environment triggers the release of iron ions, which can stimulate the production of reactive oxygen species (ROS) and induce cancer cell death through ferroptosis. Consequently, this review emphasizes these emerging physical and chemical approaches for anti-cancer therapy facilitated by magnetic nanoparticles, combining all-in-one functionalities.

Emergence of magnetic nanoparticles in photothermal and ferroptotic therapies.

Ferroptosis in hepatocellular carcinoma: from bench to bedside

The rising interest in iron vanadate nanoparticles (FeVO4 NPs) in recent years is driven by their unique physical and chemical properties, which puts them at the forefront of numerous biomedical disciplines. This review offers an in-depth exploration of the enormous biomedical possibilities linked with FeVO4 NPs. The salient aspects discussed include a description of FeVO4 NPs, along with an array of methodologies for their synthesis and characterization. An important part of this review details the nanoparticle’s electrochemical mechanisms, based on our findings we recommend promising electrochemical approaches for further investigation. Crucial to understanding their use in the biomedical field, their toxicity and biocompatibility are assessed, proving their safety for such applications. Emphasis is put on their impressive anticancer and antimicrobial attributes, showcasing their therapeutic potential. The multi-faceted nature of FeVO4 NPs is underscored further with a discussion on their potential biomedical, environmental applications, and photocatalytic activity. An exploration of other possible applications is also undertaken. Although FeVO4 NPs present a substantial efficacy, there are limitations, which are elaborated within this review. The study concludes with a constructive dialogue on prospective research directions, setting the stage for continued advancement of FeVO4 NPs in assorted biomedical applications. 

Exploring the Biomedical Potential of Iron Vanadate Nanoparticles: A Comprehensive Review

Engineering exosomes with nanomaterials usually leads to the damage of exosomal membrane and bioactive molecules. Here, pathological angiogenesis targeting exosomes with magnetic imaging, ferroptosis inducing, and immunotherapeutic properties is fabricated using a simple coincubation method with macrophages being the bioreactor. Extremely small iron oxide nanoparticle (ESIONPs) incorporated exosomes (ESIONPs@EXO) are acquired by sorting the secreted exosomes from M1-polarized macrophages induced by ESIONPs. ESIONPs@EXO suppress pathological angiogenesis in vitro and in vivo without toxicity. Furthermore, ESIONPs@EXO target pathological angiogenesis and exhibit an excellent T1-weighted contrast property for magnetic resonance imaging. Mechanistically, ESIONPs@EXO induce ferroptosis and exhibit immunotherapeutic ability toward pathological angiogenesis. These findings demonstrate that a pure biological method engineered ESIONPs@EXO using macrophages shows potential for targeted pathological angiogenesis therapy.

Iron Oxide Nanoparticles Engineered Macrophage-Derived Exosomes for Targeted Pathological Angiogenesis Therapy.

Nanotherapies are gaining increased interest for the treatment diverse diseases, particularly cancer, since they target the affected area directly, presenting higher efficacy and reduced side effects than traditional therapies. A promising nanotherapy approach is hyperthermia, where the nanoparticle can induce a local temperature increase by an external stimulus in the sick tissue to selectively kill the malignant cells. Among the diverse hyperthermia methods, photothermia is based on the absorption of light by the nanoparticles and further conversion into heat. Within the very wide range of nanostructured photothermal agents, iron oxides offer remarkable features since they are already approved by the FDA/EMA for various biomedical applications, they are biodegradable, easily manipulated using magnetic fields and can be imaged by diverse techniques. Here, we summarize the advantages of using the second biological window, both from the perspective of the skin and the optical properties of iron oxides. Further, we review the photothermal performance of iron oxide nanoparticles in the first, second and third biological windows. Overall, the results show that, for different types of iron oxide nanoparticles (Fe3O4, γ-Fe2O3, wüstite-FeO), both the heating capacity (i.e., induced temperature increase) and the photothermal conversion efficiency, η, vary in a complex way with the light wavelength, depending critically on the measurement conditions and physiochemical properties of the materials. Despite the spread in the reported photothermal properties of iron oxides, Fe3O4 particles tend to perform better than their γ-Fe2O3 counterparts, particularly in the second biological window. Interestingly, FeO, which has not been exploited so far from a photothermal perspective, shows very appealing absorption properties. Our preliminary studies using FeO/Fe3O4 core/shell nanoparticles evidence that they have excellent photothermal properties, outperforming Fe3O4 in both first and second biological windows. Finally, some applications beyond cancer treatment of iron oxide nanoparticles, exploiting the enhanced properties in the second spectral window, are discussed. 

Iron oxide nanoparticles (Fe3O4, γ-Fe2O3 and FeO) as photothermal heat mediators in the first, second and third biological windows

Nanoparticles are widely used in biological research and cancer therapy. In hepatocellular carcinoma, several nanoplatforms have been synthesized and studied to improve the drug efficacy; however, these nanoplatforms are still insufficient to eradicate tumors. Herein, we have synthesized a novel vanadium (V)-iron-oxide (ION) nanoparticle (VIO) that combines chemodynamic, photothermal, and diagnostic capacities to enhance the tumor suppression effect in one agent with multiple functions. In the in vitro models, hepatocellular carcinoma cells are significantly inhibited by VIO-based nanoagents. The mechanistic study validates that VIO increases reactive oxygen species (ROS), which led to apoptosis and ferroptosis resulting in cell death. To our surprise, VIO targets not only tumor cells but also endothelial cells. In addition to inducing cell death, VIO also blocks tube formation and cell migration in human umbilical vein endothelial cell (HUVEC) and C166 models, indicating an antiangiogenic potential. In mouse tumor models, VIO retards tumor growth and induces apoptosis in tumor tissues. Furthermore, a significant blood vessel regression is seen in VIO-treated groups accompanied with larger necrotic areas. More interestingly, the activation of photothermal therapy completely eradicates tumor tissues. Taken together, this VIO nanoplatform could be a powerful anticancer candidate for nanodrug development.

A Multifunctional Vanadium-Iron-Oxide Nanoparticle Eradicates Hepatocellular Carcinoma via Targeting Tumor and Endothelial Cells.

Glycogen phosphorylase (GP) is an essential enzyme for glycolysis via the glycogen degradation pathway. It consists of three isoforms: PYGB (brain form), PYGL (liver form) and PYGM (muscle form). Although the abnormal expression of GP is associated with a variety of tumors, its relationship with hepatocellular carcinoma (HCC) and whether it can be used as a prognostic marker of HCC remains unclear. In the present study, the expression levels of PYGB, PYGL and PYGM were analyzed. It was found that the expression levels of PYGB in tumor tissues were higher than those in normal tissues, particularly in HCC. The high expression of PYGB (hazard ratios=1.801; 95% confidence interval: 1.266-2.562) could predict the poor prognosis of HCC patients but not PYGL and PYGM. Inhibition of PYGB with GP inhibitor CP91149 significantly suppressed the HCC cell proliferation in the HCC cell model. In addition, combination treatment with sorafenib, a standard treatment for HCC, showed a great inhibition on tumor growth and angiogenesis. These findings suggested that PYGB may be used as a therapeutic and prognostic indicator for HCC.

/pdf/analysis-of-the-expression-function-and-signaling-of-16svow4t.pdf

Analysis of the expression, function and signaling of glycogen phosphorylase isoforms in hepatocellular carcinoma

https://doi.org/10.1016/j.tranon.2022.101547

Development and validation of a microenvironment-related prognostic model for hepatocellular carcinoma patients based on histone deacetylase family

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A Multifunctional Vanadium-Iron-Oxide Nanoparticle Eradicates Hepatocellular Carcinoma via Targeting Tumor and Endothelial Cells.

Analysis of the expression, function and signaling of glycogen phosphorylase isoforms in hepatocellular carcinoma

Development and validation of a microenvironment-related prognostic model for hepatocellular carcinoma patients based on histone deacetylase family