Iron Oxide Nanoclusters Research Articles

Bacterial Binding to Polydopamine-Coated Magnetic Nanoparticles.

In medical infections such as blood sepsis and in food quality control, fast and accurate bacteria analysis is required. Using magnetic nanoparticles (MNPs) for bacterial capture and concentration is very promising for rapid analysis. When MNPs are functionalized with the proper surface chemistry, they have the ability to bind to bacteria and aid in the removal and concentration of bacteria from a sample for further analysis. This study introduces a novel approach for bacterial concentration using polydopamine (pDA), a highly adhesive polymer often purported to create antibacterial and antibiofouling coatings on medical devices. Although pDA has been generally studied for its ability to coat surfaces and reduce biofilm growth, we have found that when coated on magnetic nanoclusters (MNCs), more specifically iron oxide nanoclusters, it effectively binds to and can remove from suspension some types of bacteria. This study investigated the binding of pDA-coated MNCs (pDA-MNCs) to various Gram-negative and Gram-positive bacteria, including Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and several E. coli strains. MNCs were successfully coated with pDA, and these functionalized MNCs bound a wide variety of bacterial strains. The efficiency of removing bacteria from a suspension can range from 0.99 for S. aureus to 0.01 for an E. coli strain. Such strong capture and differential capture have important applications in collecting bacteria from dilute samples found in medical diagnostics, food and water quality monitoring, and other industries.

Magnetotactic hepatocytes promote liver repopulation after transplantation

Clinical application of hepatocyte transplantation has been halted due to the low engraftment efficiency and limited proliferation capacity of donor hepatocytes in the host liver. Here, we developed a magneto-plasmonic nanohybrid to spatiotemporally drive the primary hepatocytes into the host liver under the external magnetic field that significantly improves the engraftment efficiency of donor hepatocytes. A magnetic lipid-coated-gold-nanorods/iron-oxide nanocluster (GNR-IO) (LGI) was designed for efficient magneto-actuation and photoacoustic imaging-guided cell tracking during the hepatocyte transplantation. By optimizing the concentration of LGI (100 μg /mL) and the configuration of a magnetic field (260 mT), we were able to increase the engraftment efficiency of primary hepatocytes into the host livers of Fah-/- mice, a model with the genetic deficit of fumarylacetoacetate hydrolase (FAH) resulting in liver injuries, for 3.89-fold of the control by one week of the transplantation. Further assessment of repopulation of hepatocytes in the host liver indicated the LGI (100 μg /mL) + magnetic field (260 mT) group had up to 15 % repopulation of the host liver by three-weeks-post-transplantation and reached full repopulation by 6-weeks-post-transplantation. This was 3 ∼ 5 times more rapid than the Fah-/- mice transplanted with hepatocytes without the LGI and the magnetic field. RNA-sequencing of the hepatocytes incubated with LGI indicated that the loading of LGIs enhanced the migration, survival, and engraftment of hepatocytes by regulating the tumor necrosis factor (TNF)-signaling pathway and reducing the macrophage in host liver. Furthermore, LGI-labeled hepatocytes could be tracked in host livers with photoacoustic imaging for at least one week post transplantation. Most of the LGI were cleared from the host systems via the kidneys by six weeks. The novel strategy established in this study, which utilized nanoparticles combined with the magnetic field to improve the efficiency of primary hepatocyte engraftment and repopulation, can provide a feasible scheme for the clinical application of hepatocyte transplantation in the treatment of liver failure.

Impact of tannic acid on iron oxide nanoclusters synthesized by a polyol solvothermal method

Raspberry-shaped iron oxide nanostructures (RSNs) correspond to oriented aggregated and hollow clusters of nanograins exhibiting a high saturation magnetization and a superparamagnetic behaviour. These nanostructures are promising for a wide range of applications, such as magnetic separation, catalysis, pollution control, and nanomedicine. However, for most applications, particularly nanomedecine and depollution, high colloidal stability is required, and the isoelectric point of iron oxide is around 6–7. Therefore, these nanoclusters need to be coated with a surfactant to obtain colloidal suspensions in water. Here, we have developed a one-pot polyol solvothermal synthesis process to coat these promising nanoclusters with tannic acid (TA), a natural compound with antimicrobial properties, which has been little studied with these nanoclusters. Different parameters of the synthesis were adjusted, such as the molar ratio TA:Fe, the synthesis temperature and duration. We showed that TA interferes deeply in the RSNs synthesis mechanism with the observed reduction of iron(III) to iron(II), the complexation of TA with iron, the formation of intermediate phases, as well as the growth of a parasitic iron carbonate phase and the loss of the oriented aggregation and hollowness of the iron oxide RSNs. Considering all these parameters, the optimal synthesis conditions were thus established (TA:Fe ratio = 0.010, temperature of 200°C and duration of 10.5 h), leading to RSNs with small nanograins, a rather high surface area (82 m2/g), high saturation magnetization (74 emu/g) and good colloidal stability. By combining different characterization techniques, a new synthesis mechanism was proposed different from previously established for RSNs without TA, based on strong TA-iron oxide interfaces.

Iron oxide nanoclusters formed by acid-induced in situ calcium ion cross-linking for targeted magnetic resonance imaging of glioblastoma

Contrast agents (CAs) enhanced magnetic resonance imaging (MRI) are potential candidates for the effective diagnosis of glioblastoma (GBM). However, the invasiveness and high heterogeneity of GBM interfere the effectiveness of most CAs. Compared with the conventional CAs with “always on” contrast signals, stimulus-responsive CAs that alter the MR signal in response to a specific change in their surrounding environment acquire the capability to achieve accurate diagnosis of GBM. In this study, inspired by that 1) nanocomposites can be formed by simple and controllable cross-linking anion-rich materials via multivalent cations; 2) and calcium phosphate (CaP) with good biocompatibility can be degraded triggered by acid and release divalent Ca2+, an unprecedented acid-responsive nano-CA was designed for targeted MRI of GBM. The acid-responsive targeted nano-CA (DANG-SPIO@CaP) was prepared by coating CaP on the surface of polyacrylic acid (PAA)-coated ultra-small superparamagnetic iron oxide (PAA/SPIO) nanoparticles, and then modified with the GBM-targeting DANG peptide. DANG-SPIO@CaP has good stability and relatively low T2 relaxivity at the physiological condition. However, under the weakly acidic condition in tumor microenvironment, the CaP shell of DANG-SPIO@CaP degrades, and the released Ca2+ will cross-link the exposed PAA/SPIO to form large nanoclusters with high T2 relaxivity. Consequently, DANG-SPIO@CaP can specifically navigate to GBMs, undergo the in situ acid-responsive degradation and reaggregation processes and form large nanoclusters with stronger T2 enhancing effect, allowing the locations of GBMs to be clearly recognized and even the features of different GBMs to be revealed.

Preparing iron oxide clusters surface modified Co3O4 nanoboxes by chemical vapor deposition as an efficient electrocatalyst for oxygen evolution reaction

Interface engineering is an effective way for optimizing the electronic configuration of Co3O4 to enhance the intrinsic activity of oxygen evolution reaction (OER). However, how to enrich accessible activity sites at the interface is still a challenge. Herein, Co3O4 hollow nanoboxes modified by iron oxide nanoclusters (FeOx NCs) (Fe-Co3O4 NBs) as OER electrocatalysts are prepared by a chemical vapor deposition process. Benefiting from high exposed surface area and utilization of atoms, FeOx NCs incorporation can not only regulates the spin state of Co sites, but also exposes more accessible sites for OER. Therefore, Fe-Co3O4 NBs shows excellent OER performance, manifested by the lower overpotential (η) of 265 mV at 10 mA cm−2 and smaller Tafel slope of 54.2 mV dec−1 compared to Co3O4 NBs, and many reported Co based OER electrocatalyst. Further density functional theory analysis reveals that FeOx NCs can downshift the d center of Co sites, which decreases the energy barrier of potential-determining step (PDS) for OER (*OH → *O + H+ + e−) to enhance the electroactivity. This work provides guidance for further designing high-performance OER electrocatalysts.

Expression of concern: Gadolinium embedded iron oxide nanoclusters as T1-T2 dual-modal MRI-visible vectors for safe and efficient siRNA delivery.

Expression of concern for 'Gadolinium embedded iron oxide nanoclusters as T1-T2 dual-modal MRI-visible vectors for safe and efficient siRNA delivery' by Xiaoyong Wang et al., Nanoscale, 2013, 5, 8098-8104, https://doi.org/10.1039/C3NR02797J.

Size Control of Iron Oxide (Fe<sub>3</sub>O<sub>4</sub>) Nanoclusters according to Reaction Factors and Consequent Change in Their Magnetic Attraction

Size Control of Iron Oxide (Fe<sub>3</sub>O<sub>4</sub>) Nanoclusters according to Reaction Factors and Consequent Change in Their Magnetic Attraction

CRGD-Conjugated GdIO Nanoclusters for the Theranostics of Pancreatic Cancer through the Combination of T1-T2 Dual-Modal MRI and DTX Delivery.

Clinically, magnetic resonance imaging (MRI) often uses contrast agents (CAs) to improve image contrast, but single-signal MRI CAs are often susceptible to calcification, hemorrhage, and magnetic sensitivity. Herein, iron acetylacetone and gadolinium acetylacetone were used as raw materials to synthesize a T1-T2 dual-mode imaging gadolinium-doped iron oxide (GdIO) nanocluster. Moreover, to endow the nanoclusters with targeting properties and achieve antitumor effects, the cyclic Arg-Gly-Asp (cRGD) peptide and docetaxel (DTX) were attached to the nanocluster surface, and the efficacy of the decorated nanoclusters against pancreatic cancer was evaluated. The final synthesized material cRGD-GdIO-DTX actively targeted αvβ3 on the surface of Panc-1 pancreatic cancer cells. Compared with conventional passive targeting, the enrichment of cRGD-GdIO-DTX in tumor tissues improved, and the diagnostic accuracy was significantly enhanced. Moreover, the acidic tumor microenvironment triggered the release of DTX from cRGD-GdIO-DTX, thus achieving tumor treatment. The inhibition of the proliferation of SW1990 and Panc-1 pancreatic cancer cells by cRGD-GdIO-DTX was much stronger than that by the untargeted GdIO-DTX and free DTX in vitro. In addition, in a human pancreatic cancer xenograft model, cRGD-GdIO-DTX considerably slowed tumor development and demonstrated excellent magnetic resonance enhancement. Our results suggest that cRGD-GdIO-DTX has potential applications for the precise diagnosis and efficient treatment of pancreatic cancer.

The highest oxidation state observed in graphene-supported sub-nanometer iron oxide clusters

Size-selected iron oxide nanoclusters are outstanding candidates for technological-oriented applications due to their high efficiency-to-cost ratio. However, despite many theoretical studies, experimental works on their oxidation mechanism are still limited to gas-phase clusters. Herein we investigate the oxidation of graphene-supported size-selected Fen clusters by means of high-resolution X-ray Photoelectron Spectroscopy. We show a dependency of the core electron Fe 2p3/2 binding energy of metallic and oxidized clusters on the cluster size. Binding energies are also linked to chemical reactivity through the asymmetry parameter which is related to electron density of states at the Fermi energy. Upon oxidation, iron atoms in clusters reach the oxidation state Fe(II) and the absence of other oxidation states indicates a Fe-to-O ratio close to 1:1, in agreement with previous theoretical calculations and gas-phase experiments. Such knowledge can provide a basis for a better understanding of the behavior of iron oxide nanoclusters as supported catalysts.

Modulation of blood-brain tumor barrier for delivery of magnetic hyperthermia to brain cancer.

Glioblastoma (GBM) is the most invasive brain tumor and remains lack of effective treatment. The existence of blood-brain tumor barrier (BBTB) constitutes the greatest barrier to non-invasive delivery of therapeutic agents to tumors in the brain. Here, we propose a novel approach to specifically modulate BBTB and deliver magnetic hyperthermia in a systemic delivery mode for the treatment of GBM. BBTB modulation is achieved by targeted delivering fingolimod to brain tumor region via dual redox responsive PCL-SeSe-PEG (poly (ε-caprolactone)-diselenium-poly (ethylene glycol)) polymeric nanocarrier. As an antagonist of sphingosine 1-phosphate receptor-1 (S1P1), fingolimod potently inhibits the barrier function of BBB by blocking the binding of sphingosine 1-phosphate (S1P) to S1P1 in endothelial cells. We found that the modulated BBTB showed slight expression level of tight junction proteins, allowing efficient accumulation of zinc- and cobalt- doped iron oxide nanoclusters (ZnCoFe NCs) with enhanced magnetothermal conversion efficiency into tumor tissues through the paracellular pathway. As a result, the co-delivery of heat shock protein 70 inhibitor VER-155008 with ZnCoFe NCs could realize synergistic magnetic hyperthermia effects upon exposure to an alternating current magnetic field (ACMF) in both GL261 and U87 brain tumor models. This modulation approach brings new ideas for the treatment of central nervous system diseases that require delivery of therapeutic agents across the blood-brain barrier (BBB).

Nanozyme catalytic mimetic effect of iron oxide nanoparticles hybrids with cellulosic matrices and its synergism with microorganisms

Iron Oxide Nanoparticles (IONPs) are generally assumed to be biologically inert, presenting chemical stability and low toxicity, and they can be hybridized with cellulosic matrixes aiming for biological applications (e.g. nanozymes). Two hydrothermal coprecipitation methods were applied, aiming to produce 2 different size Iron oxide nanoclusters, using ferric chloride and ferrous chloride, as well as nitrocellulose and cellulosic residues for the hybrids. The obtained materials were tested for catalytic effect in comparison and in synergy with catalase-positive P. aeruginosa, S. aureus, and B. subtilis bacterial strains. The catalytic effect was observed for all obtained materials and microorganisms, Due to the bivalent and trivalent iron molecules distributed along IONP cubic crystalline inverse spinel structures. Michaelis-Menten constant (Km) of IONP-and hybrids was higher in synergy with S. aureus in comparison with the results obtained by the microorganism alone, for instance, the best enzymatic efficiency for O2 release from hydrogen peroxide among the tested microorganisms. However, no significant difference was observed for most of the obtained materials alone. On the other hand, IONPs may help microorganisms as mimetic catalytic enzymes, when applied in synergy whit them.

Angular orientation between the cores of iron oxide nanoclusters controls their magneto–optical properties and magnetic heating functions

Oriented attachment of nanobricks into hierarchical multi-scale structures such as inorganic nanoclusters is one of the crystallization mechanisms that has revolutionized the field of nano and materials science. Herein, we show that the mosaicity, which measures the misalignment of crystal plane orientation between the nanobricks, governs their magneto-optical properties as well as the magnetic heating functions of iron oxide nanoclusters. Thanks to high-temperature and time-resolved millifluidic, we were able to isolate and characterize (structure, properties, function) the different intermediates involved in the diverse steps of the nanocluster’s formation, to propose a detailed dynamical mechanism of their formation and establish a clear correlation between changes in mosaicity at the nanoscale and their resulting physical properties. Finally, we demonstrate that their magneto-optical properties can be described using simple molecular theories.

Multifunctional Magnetic Nanoclusters Can Induce Immunogenic Cell Death and Suppress Tumor Recurrence and Metastasis.

Metastasis is the predominant cause of cancer deaths due to solid organ malignancies; however, anticancer drugs are not effective in treating metastatic cancer. Here we report a nanotherapeutic approach that combines magnetic nanocluster-based hyperthermia and free radical generation with an immune checkpoint blockade (ICB) for effective suppression of both primary and secondary tumors. We attached 2,2'-azobis(2-midinopropane) dihydrochloride (AAPH) molecules to magnetic iron oxide nanoclusters (IONCs) to form an IONC-AAPH nanoplatform. The IONC can generate a high level of localized heat under an alternating magnetic field (AMF), which decomposes the AAPH on the cluster surface and produces a large number of carbon-centered free radicals. A combination of localized heating and free radicals can effectively kill tumor cells under both normoxic and hypoxic conditions. The tumor cell death caused by the combination of magnetic heating and free radicals led to the release or exposure of various damage-associated molecule patterns, which promoted the maturation of dendritic cells. Treating the tumor-bearing mice with IONC-AAPH under AMF not only eradicated the tumors but also generated systemic antitumor immune responses. The combination of IONC-AAPH under AMF with anti-PD-1 ICB dramatically suppressed the growth of untreated distant tumors and induced long-term immune memory. This IONC-AAPH based magneto-immunotherapy has the potential to effectively combat metastasis and control cancer recurrence.

Tuning magnetic heating efficiency of colloidal dispersions of iron oxide nano-clusters by varying the surfactant concentration during solvothermal synthesis

Magnetic fluid hyperthermia (MFH) is being actively sought as a supplementary cancer therapy, where enhancing the MFH efficiency is essential for reducing dosage and field exposure. Owing to the superior magnetic properties, magnetic nano-clusters (MNCs) are being developed as MFH agents, where the role of synthesis routes, colloidal stability and magneto-structural properties on MFH efficiency requires further attention. In this article, we report the tuning of MFH efficiency of water and diethylene glycol-based magnetic nanofluids containing iron-oxide MNCs of sizes ∼ 125 to 539 nm, obtained by varying the surfactant concentration. Magnetite MNCs are prepared via solvothermal route, where the primary nano-crystallite (MNP) size is varied from 7.4 ± 0.7 to 25.0 ± 0.8 nm by reducing the sodium citrate (surfactant) concentration from 29 to 0.29 mg/mL. With decreasing surfactant concentration, the amount of sodium citrate absorbed on the surface of the freshly formed nano-seeds reduces, which lowers the electrostatic stabilization in polar media and favours the growth of larger MNPs that results in comparatively larger MNCs. Transmission electron microscopy and atomic force microscopy based studies indicate the monodisperse spherical morphology of the MNCs, consisting of several primary nano-crystallites. Room temperature isothermal magnetization measurements indicate high saturation magnetization and superparamagnetic nature of the MNCs, which are beneficial for MFH applications. Magneto-calorimetry experiments are performed for the accurate estimation of the MFH efficiency of the colloidal dispersions of the MNCs. Experimental findings indicate that the heating efficiency increases from 15.24 ± 1.22 to 193.8 ± 5.2 W/gFe (i.e., an enhancement of ∼ 12.7 times), at a field exposure condition of 33.1 kA/m and 126 kHz, when the primary nano-crystallite size is increased by ∼ 3.4 times by reducing the surfactant concentration. It is observed that the heating efficiency decreases linearly with the logarithm of surfactant concentration in all the cases, which is attributed to the variations in primary nano-crystallite sizes and the resultant magnetic losses. Magneto-calorimetric experiments, using MNCs immobilized in high viscosity agar matrix, indicate insignificant contributions from the whole-scale Brownian relaxation, and the heating efficiency is found to be solely dependent on the magnetic losses of the primary nano-crystallites. With increasing primary nano-crystallite size, augmentation of heating efficiency is due to the increase in magnetization and dynamic coercivity, which is confirmed from theoretical calculations using the high frequency hysteresis loops and sweeping rate modified Stoner Wohlfarth model. The obtained results indicate the possibility of tuning hyperthermia efficiency of MNCs by varying the surfactant concentration, which is beneficial for designing colloidally stable dispersions of MNCs with improved MFH efficiency.

Time-dependent biodistribution profiles and reaction of polyethylene glycol-coated iron oxide nanoclusters in the spleen after intravenous injection in the mice

Polyethylene glycol (PEG) is widely used polymer in the field of pharmaceutics, particularly in which related to drug delivery systems (DDS). Surface coating of the nanoparticles (NPs) with PEG (i.e. pegylation) adds novel characteristics that make their use in vivo more effective with lower cytotoxicity. The biodistribution profiles, reaction, and fate of PEG-coated NPs in vivo still unclear and need more detailed studies. Here in this study, we prepared PEG-coated iron oxide nanoclusters (PEG-coated IONCs) to investigate their biodistribution profiles and reactions in spleen after intravenous injection time-dependently. Using Prussian blue staining method as specific histochemical reaction for iron detection in the tissues, the PEG-coated IONCs were observed in a higher ratio in spleen red pulp after 1 day of injection but decreased time-dependently after 10 days and 20 days. Interestingly, PEG-coated IONCs moved from red pulp into the white pulp specially after 20 days of injection. After long time exposure (20 days), higher amount of PEG-coated IONCs was observed in the center of spleen white pulp follicle. Using histological staining, the reaction of PEG-coated IONCs with splenocytes or immune cells induced cellular abnormalities such as, nucleic acid damages, induction of megakaryocytes number, and sever vacuolation in the white pulp area specially after 20 days of injection. Histochemically, the localization of PEG-coated IONCs in the splenic parenchyma induced the level of the collagen fibers particularly after 1 day and 10 days of injection. Interestingly, cellular abnormalities in the splenic red pulp as well as collagen levels decreased after 20 days of injection due to the clearance of PEG-coated IONCs from this area. This data indicated that cytotoxicity produced by the reaction of PEG-coated IONCs in the spleen are reversible specially after 20 days of in the intravenous injection. Understanding the detailed mechanism of the fate and reaction of the coated nanomaterials after intravenous injection is important to design effective and safe DDS based NPs.

Nontoxic In Vivo Clearable Nanoparticle Clusters for Theranostic Applications.

Disintegrable inorganic nanoclusters (GIONs) with gold seed (GS) coating of an iron oxide core with a primary nanoparticle size less than 6 nm were prepared for theranostic applications. The GIONs possessed a broad near-infrared (NIR) absorbance at ∼750 nm because of plasmon coupling between closely positioned GSs on the iron oxide nanoclusters (ION) surface, in addition to the ∼513 nm peak corresponding to the isolated GS. The NIR laser-triggered photothermal response of GIONs was found to be concentration-dependent with a temperature rise of ∼8.5 and ∼4.5 °C from physiological temperature for 0.5 and 0.25 mg/mL, respectively. The nanoclusters were nonhemolytic and showed compatibility with human umbilical vein endothelial cells up to a concentration of 0.7 mg/mL under physiological conditions. The nanoclusters completely disintegrated at a lysosomal pH of 5.2 within 1 month. With an acute increase of over 400% intracellular reactive oxygen species soon after γ-irradiation and assistance from Fenton reaction-mediated supplemental oxidative stress, GION treatment in conjunction with radiation killed ∼50% of PLC/PRF/5 hepatoma cells. Confocal microscopy images of these cells showed significant cytoskeletal and nuclear damage from radiosensitization with GIONs. The cell viability further decreased to ∼10% when they were sequentially exposed to the NIR laser followed by γ-irradiation. The magnetic and optical properties of the nanoclusters enabled GIONs to possess a T2 relaxivity of ∼223 mM-1 s-1and a concentration-dependent strong photoacoustic signal toward magnetic resonance and optical imaging. GIONs did not incur any organ damage or evoke an acute inflammatory response in healthy C57BL/6 mice. Elemental analysis of various organs indicated differential clearance of gold and iron via both renal and hepatobiliary routes.

Biodegradable Protein-Stabilized Inorganic Nanoassemblies for Photothermal Radiotherapy of Hepatoma Cells.

Inorganic nanomaterials require optimal engineering to retain their functionality yet can also biodegrade within physiological conditions to avoid chronic accumulation in their native form. In this work, we have developed gelatin-stabilized iron oxide nanoclusters having a primary crystallite size of ∼10 nm and surface-functionalized with indocyanine green (ICG)-bound albumin-stabilized gold nanoclusters (Prot-IONs). The Prot-IONs are designed to undergo disintegration in an acidic microenvironment of tumor in the presence of proteolytic enzymes within 72 h. These nanoassemblies demonstrate bio- and hemocompatibility and show significant photothermal efficiency due to strong near infrared absorption contributed by ICG. The surface gold nanoclusters could efficiently sensitize hepatoma cells to γ-irradiation with substantial cytoskeletal and nuclear damage. Sequential irradiation of Prot-ION-treated cancer cells with near infrared (NIR) laser (λ = 750 nm) and γ-irradiation could cause ∼90% cell death compared to single treatment groups at a lower dose of nanoparticles. The superparamagnetic nature of Prot-IONs imparted significant relaxivity (∼225 mM–1 s–1) for T2-weighted magnetic resonance imaging. Additionally, they could also be engaged as photoacoustic and NIR imaging contrast agents. This work demonstrates bioeliminable inorganic nanoassemblies with significant theranostic potential.

Pulmonary Delivery of Theranostic Nanoclusters for Lung Cancer Ferroptosis with Enhanced Chemodynamic/Radiation Synergistic Therapy.

Inefficient tumor accumulation and penetration remain as the main challenges to therapy efficacy of lung cancer. Local delivery of smart nanoclusters can increase drug penetration and provide superior antitumor effects than systemic routes. Here, we report self-assembled pH-sensitive superparamagnetic iron oxide nanoclusters (SPIONCs) that enhance in situ ferroptosis and apoptosis with radiotherapy and chemodynamic therapy. After pulmonary delivery in orthotopic lung cancer, SPIONCs disintegrate into smaller nanoparticles and release more iron ions in an acidic microenvironment. Under single-dose X-ray irradiation, endogenous superoxide dismutase converts superoxide radicals produced by mitochondria to hydrogen peroxide, which in turn generates hydroxyl radicals by the Fenton reaction from iron ions accumulated inside the tumor. Finally, irradiation and iron ions enhance tumor lipid peroxidation and induce cell apoptosis and ferroptosis. Thus, rationally designed pulmonary delivered nanoclusters provide a promising strategy for noninvasive imaging of lung cancer and synergistic therapy.

Mag-spinner: a next-generation Facile, Affordable, Simple, and porTable (FAST) magnetic separation system.

Mag-spinner, a system in which magnets are combined with a spinner system, is a new type of magnetic separation system for the preprocessing of biological and medical samples. Interference by undesired components restricts the detection accuracy and efficiency. Thus, the development of appropriate separation techniques is required for better detection of the desired targets, to enrich the target analytes and remove the undesired components. The strong response of iron oxide nanoclusters can successfully capture the targets quickly and with high efficiency. As a result, cancer cells can be effectively separated from blood using the developed mag-spinner system. Indeed, this system satisfies the requirements for desirable separation systems, namely (i) fast sorting rates, (ii) high separation efficiency, (iii) the ability to process native biological fluids, (iv) simple operating procedures, (v) low cost, (vi) operational convenience, and (vii) portability. Therefore, this system is widely applicable to sample preparation without limitations on place, cost, and equipment.

Tumor-penetrating iron oxide nanoclusters for T1/T2 dual mode MR imaging-guided combination therapy.

Emerging nanotheranostic systems have promoted the development of dual-mode imaging techniques (i.e. T1/T2-weighted MRI) to meet the increasing requirements of accurate personalized treatment for cancer. Nevertheless, slight tumor accumulation and poor penetration have limited the efficacy of dual-mode theranostic agents. Furthermore, under the premise of guaranteeing imaging capability, most current research studies hardly focused on optimizing theranostic agents to achieve considerable therapeutic effects. Here, we developed a hyaluronic acid (HA)-stabilized iron oxide nanocluster (Fe2O3@PFDH NC) as an intelligent-degradable theranostic nanoagent for dual-mode MRI-guided chemo-photothermal therapy. The obtained Fe2O3@PFDH NC with high longitudinal and transverse relaxivities offers strong contrast in T1/T2-weighted MR imaging. Meanwhile, according to MR images, the intravenous Fe2O3@PFDH NC could accumulate at the hyaluronidase-rich tumor location gradually. More interestingly, it could break into smaller nanoparticles with quick DOX release for deep penetration, accompanied by highly effective photothermal ablation of the tumor under laser irradiation. In conclusion, the versatile tumor-penetrating Fe2O3@PFDH nanocluster could serve as a T1/T2 dual-mode MRI contrast agent with highly effective combination chemo-photothermal therapy, and would be an ideal theranostic nanocarrier with translational potential for future clinical diagnosis and treatment of cancer.