Recent trends in preparation and biomedical applications of iron oxide nanoparticles.
Journal of nanobiotechnology
The iron oxide nanoparticles (IONPs), possessing both magnetic behavior and semiconductor property, have been extensively used in multifunctional biomedical fields due to their biocompatible, biodegradable and low toxicity, such as anticancer, antibacterial, cell labelling activities. Nevertheless, there are few IONPs in clinical use at present. Some IONPs approved for clinical use have been withdrawn due to insufficient understanding of its biomedical applications. Therefore, a systematic summary of IONPs' preparation and biomedical applications is crucial for the next step of entering clinical practice from experimental stage. This review summarized the existing research in the past decade on the biological interaction of IONPs with animal/cells models, and their clinical applications in human. This review aims to provide cutting-edge knowledge involved with IONPs' biological effects in vivo and in vitro, and improve their smarter design and application in biomedical research and clinic trials.
10.1186/s12951-023-02235-0
Iron oxide magnetic aggregates: Aspects of synthesis, computational approaches and applications.
Advances in colloid and interface science
Superparamagnetic magnetite nanoparticles have been central to numerous investigations in the past few decades for their use in many applications, such as drug delivery, medical diagnostics, magnetic separation, and material science. However, the properties of single magnetic nanoparticles are sometimes not sufficient to accomplish tasks where a strong magnetic response is required. In light of this, aggregated magnetite nanoparticles have been proposed as an alternative advanced material, which may expand and combine some of the advantages of single magnetic nanoparticles, including superparamagnetism, with an enhanced magnetic moment and increased colloidal stability. This review comprehensively discusses the current literature on aggregates made of magnetic iron oxide nanoparticles. This review is divided into three sections. First, the current synthetic strategies for magnetite nanoparticle aggregates are discussed, together with the influence of different stabilizers on the primary crystals and the final aggregate size and morphology. The second section is dedicated to computational approaches, such as density functional methods (which permit accurate predictions of electronic and magnetic properties and shed light on the behavior of surfactant molecules on iron oxide surfaces) and molecular dynamics simulations (which provide additional insight into the influence of ligands on the surface chemistry of iron oxide nanocrystals). The last section discusses current and possible future applications of iron oxide magnetic aggregates, including wastewater treatment, water purification, medical applications, and magnetic aggregates for materials displaying structural colors.
10.1016/j.cis.2023.103056
Photothermal Ferrotherapy - Induced Immunogenic Cell Death via Iron-Based Ternary Chalcogenide Nanoparticles Against Triple-Negative Breast Cancer.
Small (Weinheim an der Bergstrasse, Germany)
Triple-negative breast cancer (TNBC) is highly malignant and prone to recurrence and metastasis. Patients with TNBC have limited therapeutic options, often resulting in poor prognosis. Some new treatments for TNBC have been considered in the past decade, such as immunotherapy, photothermal therapy (PTT), and ferroptosis therapy, that allow the rapid and minimally invasive ablation of cancer. However, a multifunctional nanodrug system with more potent efficacy for TNBC is still needed. The use of iron-based ternary chalcogenide nanoparticles (NPs), namely AgFeS, is reported, which synergistically combines photothermal therapy, ferrotherapy, and immunotherapy in one system for the treatment of TNBC. AgFeS possesses excellent photothermal conversion performance for tumor near-infrared (NIR) phototherapy. Upon photoirradiation, these NPs generate heat, accelerate the release of iron ions, and effectively catalyze the Fenton reaction, resulting in cell apoptosis and ferroptosis. Additionally, AgFeS promotes the release of tumor-specific antigens and triggers an immune response via immunogenic cell death (ICD), thereby providing unique synergistic mechanisms for cancer therapy. The present study demonstrates the great potential of iron-based ternary chalcogenide as a new therapeutic platform for a combination of photothermal therapy, ferrotherapy, and immunotherapy for the suppression of TNBC.
10.1002/smll.202306766
Fortification of Iron Oxide as Sustainable Nanoparticles: An Amalgamation with Magnetic/Photo Responsive Cancer Therapies.
International journal of nanomedicine
Due to their non-toxic function in biological systems, Iron oxide NPs (IO-NPs) are very attractive in biomedical applications. The magnetic properties of IO-NPs enable a variety of biomedical applications. We evaluated the usage of IO-NPs for anticancer effects. This paper lists the applications of IO-NPs in general and the clinical targeting of IO-NPs. The application of IONPs along with photothermal therapy (PTT), photodynamic therapy (PDT), and magnetic hyperthermia therapy (MHT) is highlighted in this review's explanation for cancer treatment strategies. The review's study shows that IO-NPs play a beneficial role in biological activity because of their biocompatibility, biodegradability, simplicity of production, and hybrid NPs forms with IO-NPs. In this review, we have briefly discussed cancer therapy and hyperthermia and NPs used in PTT, PDT, and MHT. IO-NPs have a particular effect on cancer therapy when combined with PTT, PDT, and MHT were the key topics of the review and were covered in depth. The IO-NPs formulations may be uniquely specialized in cancer treatments with PTT, PDT, and MHT, according to this review investigation.
10.2147/IJN.S404394
Radiosensitizing effects of heparinized magnetic iron oxide nanoparticles in colon cancer.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
The combination of radiation treatment and chemotherapy is currently the standard for management of cancer patients. However, safe doses do not often provide effective therapy, then pre-treated patients are forced to repeat treatment with often already increased tumor resistance to drugs and irradiation. One of the solutions we suggest is to improve primary course of radiation treatment via enhancing radiosensitivity of tumors by magnetic-guided iron oxide nanoparticles (magnetite). We obtained spherical heparinized iron oxide nanoparticles (hIONPs, ∼20 nm), characterized it by TEM, Infrared spectroscopy and DLS. Then hIONPs cytotoxicity was assessed for colon cancer cells (XTT assay) and cellular uptake of nanoparticles was analyzed with X-ray fluorescence. Combination of ionizing radiation (IR) and hIONPs in vitro caused an increase of G2/M arrest of cell cycle, mitotic errors and decrease in survival (compared with samples exposed to IR and hIONPs separately). The promising results were shown for magnetic-guided hIONPs in CT26-grafted BALB/C mice: the combination of intravenously administrated hIONPs and IR showed 20,8% T/C ratio (related to non-treated mice), while single radiation had no shown significant decrease in tumor growth (72,4%). Non-guided by magnets hIONPs with IR showed 57,9% of T/C. This indicates that ultra-small size and biocompatible molecule are not the key to successful nano-drug design, in each case, delivery technologies need to be improved when transferred to in vivo model.
10.1016/j.biopha.2024.116668
Renal-clearable porous hollow copper iron oxide nanoparticles for trimodal chemodynamic-photothermal-chemo anti-tumor therapy.
Nanoscale
Multifunctional nanoplatforms with the synergistic effects of multiple therapeutic modalities have become a research focus due to their superior anti-tumor properties over single therapeutic modalities. Herein, we developed around 14 nm porous hollow copper iron oxide nanoparticles (PHCuFeNPs) with pore sizes of around 2-3 nm as a cisplatin carrier and photothermal therapeutic agent. The PHCuFeNPs were synthesized a galvanic reaction between CuS nanoparticles and iron pentacarbonyl (Fe(CO)) followed by etching in the organic phase to make the pores. They were stable under normal physiological conditions, but the pores were etched in a weak acidic tumor microenvironment, resulting in the controlled release of Cu and Fe ions for enhanced chemodynamic therapy and accelerated cisplatin release for chemotherapy. Under 980 nm laser irradiation, the PHCuFeNPs could effectively heat up to further promote the release process for synergistic therapy. Besides, they were proved to mediate immunogenic cell death to activate the immune system for potential immunotherapy. Together with their ability to degrade into fragments for fast renal metabolism, we believe that these PHCuFeNPs could provide a biocompatible and efficient multi-antitumor therapeutic approach.
10.1039/d2nr06224k
Photothermal and ferroptosis synergistic therapy for liver cancer using iron-doped polydopamine nanozymes.
Colloids and surfaces. B, Biointerfaces
An innovative nanozyme, iron-doped polydopamine (Fe-PDA), which integrates iron ions into a PDA matrix, conferred peroxidase-mimetic activity and achieved a substantial photothermal conversion efficiency of 43.5 %. Fe-PDA mediated the catalysis of HO to produce toxic hydroxyl radicals (•OH), thereby facilitating lipid peroxidation in tumour cells and inducing ferroptosis. Downregulation of solute carrier family 7 no. 11 (SLC7A11) and solute carrier family 3 no. 2 (SLC3A2) in System Xc- resulted in decreased intracellular glutathione (GSH) production and inactivation of the nuclear factor erythroid 2-related factor 2 (NRF2)-glutathione peroxidase 4 (GPX4) pathway, contributing to ferroptosis. Moreover, the application of photothermal therapy (PTT) enhanced the effectiveness of chemodynamic therapy (CDT), accelerating the Fenton reaction for targeted tumour eradication while sparing adjacent non-cancerous tissues. In vivo experiments revealed that Fe-PDA significantly hampered tumour progression in mice, emphasizing the potential of the dual-modality treatment combining CDT and PTT for future clinical oncology applications.
10.1016/j.colsurfb.2024.113911
Tumor Acidic Microenvironment-Responsive Promodulator Iron Oxide Nanoparticles for Photothermal-Enhanced Chemodynamic Immunotherapy of Cancer.
ACS biomaterials science & engineering
Cancer nanomedicine combined with immunotherapy has emerged as a promising strategy for the treatment of cancer. However, precise regulation of the activation of antitumor immunity in targeting tissues for safe and effective cancer immunotherapy remains challenging. Herein, we report a tumor acidic microenvironment-responsive promodulator iron oxide nanoparticle (termed as FGR) with pH-activated action for photothermal-enhanced chemodynamic immunotherapy of cancer. FGR is formed via surface-modifying iron oxide nanoparticles with a dextran-conjugated Toll-like receptor agonist (R848) containing an acid-labile bond. In an acidic tumor microenvironment, the acid-responsive bonds are hydrolyzed to trigger the specific release of R848 to promote the maturation of dendritic cells. In addition, iron oxide nanoparticles within FGR exert photothermal and chemodynamic effects under near-infrared laser irradiation to directly kill tumor cells and induce immunogenic cell death. The synergistic effect of the released immunogenic factors and the acid-activated TLR7/8 pathway stimulates the formation of strong antitumor immunity, resulting in increased infiltration of cytotoxic CD8 T cells into tumor tissues. As a result, FGR achieves acid-responsive on-demand release and activation of modulators in tumor sites and mediates photothermal-enhanced chemodynamic immunotherapy to inhibit the growth and metastasis of melanoma. Therefore, this work proposes a general strategy for designing prodrug nanomedicines to accurately regulate cancer immunotherapy.
10.1021/acsbiomaterials.2c01287
Zn doped iron oxide nanoparticles with high magnetization and photothermal efficiency for cancer treatment.
Journal of materials chemistry. B
Magnetic nanoparticles (NPs) are powerful agents to induce hyperthermia in tumours upon the application of an alternating magnetic field or an infrared laser. Dopants have been investigated to alter different properties of materials. Herein, the effect of zinc doping into iron oxide NPs on their magnetic properties and structural characteristics has been investigated in-depth. A high temperature reaction with autogenous pressure was used to prepare iron oxide and zinc ferrite NPs of same size and morphology for direct comparison. Pressure was key in obtaining high quality nanocrystals with reduced lattice strain (27% less) and enhanced magnetic properties. ZnFeO NPs with small size of 10.2 ± 2.5 nm and very high saturation magnetisation of 142 ± 9 emu g were obtained. Aqueous dispersion of the NPs showed long term magnetic (up to 24 months) and colloidal stability (at least 6 d) at physiologically mimicking conditions. The samples had been kept in the fridge and had been stable for four years. The biocompatibility of ZnFeO NPs was next evaluated by metabolic activity, membrane integrity and clonogenic assays, which show an equivalence to that of iron oxide NPs. Zinc doping decreased the bandgap of the material by 22% making it a more efficient photothermal agent than iron oxide-based ones. Semiconductor photo-hyperthermia was shown to outperform magneto-hyperthermia in cancer cells, reaching the same temperature 17 times faster whilst using 20 times less material (20 mg ml. 1 mg ml). Magnetothermal conversion was minimally hindered in the cellular confinement whilst photothermal efficiency remained unchanged. Photothermia treatment alone achieved 100% cell death after 10 min of treatment compared to only 30% cell death achieved with magnetothermia at clinically relevant settings for each at their best performing concentration. Altogether, these results suggest that the biocompatible and superparamagnetic zinc ferrite NPs could be a next biomaterial of choice for photo-hyperthermia, which could outperform current iron oxide NPs for magnetic hyperthermia.
10.1039/d2tb01338j
Gold and Iron Oxide Nanoparticle Assemblies on Turnip Yellow Mosaic Virus for In-Solution Photothermal Experiments.
Nanomaterials (Basel, Switzerland)
The ability to construct three-dimensional architectures via nanoscale engineering is important for emerging applications in sensors, catalysis, controlled drug delivery, microelectronics, and medical diagnostics nanotechnologies. Because of their well-defined and highly organized symmetric structures, viral plant capsids provide a 3D scaffold for the precise placement of functional inorganic particles yielding advanced hierarchical hybrid nanomaterials. In this study, we used turnip yellow mosaic virus (TYMV), grafting gold nanoparticles (AuNP) or iron oxide nanoparticles (IONP) onto its outer surface. It is the first time that such an assembly was obtained with IONP. After purification, the resulting nano-biohybrids were characterized by different technics (dynamic light scattering, transmission electron microcopy, X-ray photoelectron spectroscopy…), showing the robustness of the architectures and their colloidal stability in water. In-solution photothermal experiments were then successfully conducted on TYMV-AuNP and TYMV-IONP, the related nano-biohybrids, evidencing a net enhancement of the heating capability of these systems compared to their free NP counterparts. These results suggest that these virus-based materials could be used as photothermal therapeutic agents.
10.3390/nano13182509
Iron-based magnetic nanocomplexes for combined chemodynamic and photothermal cancer therapy through enhanced ferroptosis.
Biomaterials advances
Chemodynamic therapy (CDT) guided by Fenton chemistry and iron-containing materials can induce ferroptosis as a prospective cancer treatment method, but the inefficient Fe/Fe conversion restricts the monotherapeutic performances. Here, an iron-based nanoplatform (FeO-SRF@FeTA) including a magnetic core and a reductive film is developed for combined CDT and photothermal therapy (PTT) through ferroptosis augmentation. The inner iron oxide core serves as a photothermal transducer, a magnet-responsive module, and an iron reservoir for CDT. The coated Fe-tannic acid film (FeTA) provides extra iron and reductants for Fe/Fe conversion acceleration, and functions as a door keeper for the pH- and light-responsive release of the embedded ferroptosis inducer sorafenib (SRF). The in vitro results demonstrate that the iron-based nanocomplexes promote the production of lipid peroxide through the amplified Fenton activity, and downregulate glutathione involved in lipid peroxide repair system through the responsively released SRF. Upon accumulation in tumor by magnetic targeting and sequential laser irradiation locoregionally, FeO-SRF@FeTA nanocomplexes present prominent in vivo anticancer efficacy by leveraging PTT and CDT-enhanced ferroptosis.
10.1016/j.bioadv.2024.214046
Iron-based nanoparticles for MR imaging-guided ferroptosis in combination with photodynamic therapy to enhance cancer treatment.
Chen Qifang,Ma Xianbin,Xie Li,Chen Wenjie,Xu Zhigang,Song Erqun,Zhu Xiaokang,Song Yang
Nanoscale
Ferroptosis therapy, which applies ferroptotic inducers to produce lethal lipid peroxidation and induce the death of tumor cells, is regarded as a promising therapeutic strategy for cancer treatment. However, there is still a challenge regarding how to increase reactive oxygen species (ROS) accumulation in the tumor microenvironment (TME) to enhance antitumor efficacy. Herein, we designed a nanosystem coated with the FDA approved poly(lactic-co-glycolic acid) (PLGA) containing ferrous ferric oxide (Fe3O4) and chlorin E6 (Ce6) for synergistic ferroptosis-photodynamic anticancer therapy. The Fe3O4-PLGA-Ce6 nanosystem can dissociate in the acidic TME to release ferrous/ferric ions and Ce6. Then, the Fenton reaction between the released ferrous/ferric ions and intracellular excess hydrogen peroxide can occur to produce hydroxyl radicals (˙OH) and induce tumor cell ferroptosis. The released Ce6 can increase the generation and accumulation of ROS under laser irradiation to offer photodynamic therapy, which can boost ferroptosis in 4T1 cells. Moreover, magnetic monodisperse Fe3O4 loading provides excellent T2-weighted magnetic resonance imaging (MRI) properties. The Fe3O4-PLGA-Ce6 nanosystem possesses MRI ability and highly efficient tumor suppression with high biocompatibility in vivo due to the synergism of photodynamic and ferroptosis antitumor therapies.
10.1039/d0nr08757b
Bio-synthesized iron oxide nanoparticles for cancer treatment.
Alphandéry Edouard
International journal of pharmaceutics
Various living organisms, such as bacteria, plants, and animals can synthesize iron oxide nanoparticles (IONP). The mechanism of nanoparticle (NP) formation is usually described as relying on the reduction of ferric/ferrous iron ions into crystallized nanoparticulate iron that is surrounded by an organic stabilizing layer. The properties of these NP are characterized by a composition made of different types of iron oxide whose most stable and purest one appears to be maghemite, by a size predominantly comprised between 5 and 380 nm, by a crystalline core, by a surface charge which depends on the nature of the material coating the iron oxide, and by certain other properties such as a sterility, stability, production in mass, absence of aggregation, that have apparently only been studied in details for IONP synthesized by magnetotactic bacteria, called magnetosomes. In the majority of studies, bio-synthesized IONP are described as being biocompatible and as not inducing cytotoxicity towards healthy cells. Anti-tumor activity of bio-synthesized IONP has mainly been demonstrated in vitro, where this type of NP displayed cytotoxicity towards certain tumor cells, e.g. through the anti-tumor activity of IONP coating or through IONP anti-oxidizing property. Concerning in vivo anti-tumor activity, it was essentially highlighted for magnetosomes administered in different types of glioblastoma tumors (U87-Luc and GL-261), which were exposed to a series of alternating magnetic field applications, resulting in mild hyperthermia treatments at typical temperatures of 41-45 °C, leading to the full disappearance of these tumors without any observable side effects.
10.1016/j.ijpharm.2020.119472