Intracellular Criegee's mechanism-based synergistic ozone therapy mediated by oleogels for cancer treatment.

Broad cellular components-initiated efficient chemical reactions that occur in malignant cells may contribute to exploring emerging strategies for cancer treatment. Herein, an ozonated oleogel (OG(O)) was developed to achieve cancer ozone therapy (O3-T) based on intracellular Criegee's reaction. By integrating the chemo-drug, the ozone-loaded oleogel (Dox@OG(O)) was prepared as a chemotherapeutic agent for local O3-T, associated with chemotherapy (CT)/radiotherapy (RT)/immunotherapy and wound healing. The in vitro results showed that, Dox@OG(O) could achieve high ozone loading efficiency and ensure its stability. This Oleogel-mediated O3-T could directly destroy tumor cells via intracellular Criegee's reaction occurred on cell membranes, as well as the effects of tumor microenvironment (TME) regulation by the generation of oxygen/reactive oxygen species (ROS) and depletion of glutathione (GSH). Meanwhile, under the stimulation of X-ray, an accelerated free radical's production was observed, further combined with the radio-sensitivity after TME regulation, an effective anti-tumor effect would be achieved. Further on, in vivo results demonstrated that the locally implanted Dox@OG(O) could effectively inhibit the growth of both primary and secondary tumors. Considering these results above, it will serve as inspiration for future studies investigating of O3-T, especially for postoperative skin diseases.

Cancer nutritional-immunotherapy with NIR-II laser-controlled ATP release based on material repurposing strategy.

Enlightened by the great success of the drug repurposing strategy in the pharmaceutical industry, in the current study, material repurposing is proposed where the performance of carbonyl iron powder (CIP), a nutritional intervention agent of iron supplement approved by the US FDA for iron deficiency anemia in clinic, was explored in anti-cancer treatment. Besides the abnormal iron metabolic characteristics of tumors, serving as potential targets for CIP-based cancer therapy under the repurposing paradigm, the efficacy of CIP as a catalyst in the Fenton reaction, activator for dihydroartemisinin (DHA), thus increasing the chemo-sensitivity of tumors, as well as a potent agent for NIR-II photothermal therapy (PTT) was fully evaluated in an injectable alginate hydrogel form. The CIP-ALG gel caused a rapid temperature rise in the tumor site under NIR-II laser irradiation, leading to complete ablation in the primary tumor. Further, this photothermal-ablation led to the significant release of ATP, and in the bilateral tumor model, both primary tumor ablation and inhibition of secondary tumor were observed simultaneously under the synergistic tumor treatment of nutritional-photothermal therapy (NT/PTT). Thus, material repurposing was confirmed by our pioneering trial and CIP-ALG-meditated NT/PTT/immunotherapy provides a new choice for safe and efficient tumor therapy.

Self-Monitoring Theranostic Nanomaterials: Emerging Visual Agents for Real-Time Monitoring of Tumor Treatment Processes.

Self-monitoring in tumor therapy is a concept that allows for real-time monitoring of the location and state of applied nanomaterials. This monitoring relies on dynamic signals, such as wave or magnetic signals, which vary in response to changes in the location and state of nanomaterials. Dynamic changes in nanomaterials can be monitored using dynamic signals, making it possible to determine and control the treatment process. Theranostic nanomaterials, which possess unique physical and chemical properties, have recently been explored as a viable option for self-monitoring. With the help of self-monitoring, theranostic nanomaterials can guide themselves to achieve region-selective treatment with higher controllability and safety. In this review, self-monitoring theranostic nanomaterials will be introduced in three parts according to their roles during therapy: tumor accumulation, tumor therapy, and metabolism. The limitations and future challenges of current self-monitoring theranostic nanomaterials will also be discussed.

Scalable and Flexible Multi-Layer Prismatic Photonic Metamaterial Film for Efficient Daytime Radiative Cooling.

To maintain a comfortable indoor living environment in low latitude or tropical regions, humans consume significant amounts of electrical energy in air conditioning, leading to substantial CO2 emissions. Passive daytime radiative cooling (PDRC) allows objects to cool down during the daytime without any energy consumption by dissipating heat through the atmospheric transparency window (8-13 µm) to outer space, which has garnered significant attention. However, the practical applications of common PDRC materials are hindered by their poor optical selectivity and high-reflective silver backing. Additionally, the availability of artificial photon emitters with complex structures and excellent performance is also limited by their high cost. Herein, a novel multilayer prismatic photonic metamaterial film without any silver reflector, easily scalable and produced by a roll-to-roll method is demonstrated, which exhibits ≈96.4% sunlight reflectance (0.3-2.5 µm) and ≈97.2% emissivity in mid-infrared (IR) (8-13 µm). At an average solar intensity of ≈920 W m-2 , it is on average 6.8 °C below ambient temperature during the day and theoretically yields a radiative cooling power of 88.9 W m-2 . Furthermore, the film exhibits excellent hydrophobicity, superior flexibility, and robust mechanical strength, providing an attractive and viable pathway for practical applications addressing the pressing challenges of climate and energy issues.

Physical Dissolution Combined with Photodynamic Depletion: A Two-Pronged Nanoapproach for Deoxygenation-Driven and Hypoxia-Activated Prodrug Therapy.

Hypoxia may enhance the chemoresistance of cancer cells and can significantly compromise the effectiveness of chemotherapy. Many efforts have been made to relieve or reverse hypoxia by introducing more oxygen into the tumor microenvironment (TME). Acting in a diametrically opposite way, in the current study, a novel nanocarrier was designed to further exhaust the oxygen level of the hypoxic TME. By creating such an oxygen depleted TME, the hypoxia-selective cytotoxin can work effectively, and oxygen exhaustion triggered chemotherapy can be achieved. Herein, deoxygenation agent, FDA-approved perfluorocarbon (PFC) and photosensitizer indocyanine green (ICG) for oxygen depletion, along with the hypoxia-activating drug tirapazamine (TPZ), were coincorporated within the poly(lactic-co-glycolic acid) (PLGA) nanoemulsion (ICG/TPZ@PPs) for the treatment of hypoxic tumors. Following hypoxia amplifying through physical oxygen dissolution and photodynamic depletion in tumors, hypoxic chemotherapy could be effectively activated to improve multitreatment synergy. After achieving local tumor enrichment, PFC-mediated oxygen dissolution combined with further ICG-mediated photodynamic therapy (PDT) under near-infrared (NIR) laser irradiation could induce enhanced hypoxia, which would activate the antitumor activity of codelivered TPZ to synergize cytotoxicity. Remarkably, in vivo experimental results exhibited that deoxygenated ICG/TPZ@PPs-based photothermal therapy (PTT), PDT, and hypoxia activated chemotherapy have an excellent synergistic ablation of tumors without obvious side effects, and therefore, a broad prospect of application of this nanocarrier could be expected.

Enhanced Stress Stability in Flexible Co/Pt Multilayers with Strong Perpendicular Magnetic Anisotropy.

Due to the magnetoelastic coupling, the magnetic properties of many flexible magnetic films (such as Fe, Co, and Ni) are sensitive to mechanical stress, which deteriorates the performance of flexible magnetoelectronic devices. We show that by stacking Co and Pt alternatively to form multilayers with strong perpendicular magnetic anisotropy (PMA), both magnetic hysteresis and magnetic domain measurements reveal robust PMA against external stress. As the PMA weakens at increased Co thickness, the magnetic anisotropy is vulnerable to external stress. These results were understood based on a micromagnetic model, which suggests that the strength of magnetoelastic anisotropy with respect to initial effective magnetic anisotropy affects the stress-stability of the film. Although the stress coefficient of magnetoelastic anisotropy is enhanced at reduced Co thickness, the concomitant increase of initial effective magnetic anisotropy guarantees a robust PMA against external stress. Our results provide a route to constructing flexible magnetoelectronic devices with enhanced stress stability.

Redox Homeostasis Disruptors Based on Metal-Phenolic Network Nanoparticles for Chemo/Chemodynamic Synergistic Tumor Therapy through Activating Apoptosis and Cuproptosis.

The combination of chemo/chemodynamic therapy is a promising strategy for improving antitumor efficacy. Herein, metal-phenolic network nanoparticles (NPs) self-assembled from copper ions and gallic acid (Cu-GA) are developed to evoke apoptosis and cuproptosis for synergistic chemo/chemodynamic therapy. The Cu-GA NPs are biodegraded in response to the highly expressed glutathione (GSH) in tumor cells, resulting in the simultaneous release of Cu+ and GA. The intracellular GSH content is dramatically reduced by the released GA, rendering the tumor cells incapable of scavenging reactive oxygen species (ROS) and more susceptible to cuproptosis. Meanwhile, ROS levels within the tumor cells are significantly increased by the Fenton-like reaction of released Cu+ , which disrupts redox homeostasis and achieves apoptosis-related chemodynamic therapy. Moreover, massive accumulation of Cu+ in the tumor cells further induces aggregation of lipoylated dihydrolipoamide S-acetyltransferase and downregulation of iron-sulfur cluster protein, activating cuproptosis to enhance the antitumor efficacy of Cu-GA NPs. The experiments in vivo further demonstrate that Cu-GA NPs exhibited the excellent biosafety and superior antitumor capacity, which can efficiently inhibit the growth of tumors due to the activation by the tumor specific GSH and hydrogen peroxide. These Cu-based metal-phenolic network NPs provide a potential strategy to build up efficient and safe cancer therapy.

Acidity-Triggered Charge-Convertible Conjugated Polymer for Dihydroartemisinin Delivery and Tumor-Specific Chemo-Photothermal Therapy.

Since the nonspecificity and nonselectivity of traditional treatment models lead to the difficulty of cancer treatment, nanobased strategies are needed to fill in the gaps of current approaches. Herein, a tumor microenvironment (TME)-responsive chemo-photothermal treatment model was developed based on dihydroartemisinin (DHA)-loaded conjugated polymers (DHA@PLGA-PANI). The synthesized DHA@PLGA-PANI exhibited enhanced photothermal properties under mild-acidic conditions and thus triggered local heat at the tumor site. Meanwhile, these iron-doped conjugated polymers of PLGA-PANI were used as the source of Fe, and benefiting from the Fe-dependent cytotoxicity of DHA, the burst of free radicals could be generated in tumors. Therefore, the combination of TME-responsive chemo-photothermal therapy could achieve effective tumor efficacy.

Preparation of Densified Fine-Grain High-Frequency MnZn Ferrite Using the Cold Sintering Process.

The densified MnZn ferrite ceramics were prepared using the cold sintering process under pressure, with an acetate ethanol solution used as the transient solvent. The effects of the transient solvent, the pressure and annealing temperature on the density, and the micromorphology and magnetic properties of the sintered MnZn ferrites were studied. The densified MnZn ferrite was obtained using the cold sintering process and its relative density reached up to 85.4%. The transient solvent and high pressure are essential to the cold sintering process for MnZn ferrite. The annealing treatment is indispensable in obtaining the sample with the higher density. The relative density was further increased to 97.2% for the sample annealed at 950 °C for 6 h. The increase in the annealing temperature reduces the power loss at high frequencies.

NIR absorptive croconic acid/quercetin/CaO2 nanoplatform for tumor calcium overload therapy combined mild photothermal therapy.

With excellent biocompatibility, stable chemical and optical properties, small organic molecules-based agents have always been a research hotspot in cancer photothermal therapy (PTT). In this work, a novel croconic acid-based molecule (CR) was designed and synthesized as an ideal photothermal agent (PTA), which showed abundant near-infrared (NIR) light absorption, high photothermal conversion ability, and excellent photothermal stability. By loading CR and quercetin (Qu) in CaO2, and coated with DSPE-PEG2000, a multifunctional theranostic nanoparticle (CCQ) was successfully prepared for calcium overloading mitochondrial metabolism inhibition synergetic mild PTT. Upon entering tumor microenvironment, CCQ can produce abundant H2O2 and a large amount of calcium ions, which lead to the imbalance of calcium concentration in the internal environment of tumor cells and induced mitochondrial apoptosis. With the existence of Qu, CCQ can effectively inhibit the expression of heat shock proteins (Hsp) during the PTT process, which weaken the heat resistance of tumors, ablate tumors at lower temperature (~45 °C), and reduce the damage to normal tissues. Guided by photoacoustic imaging (PAI), CCQ showed excellent multimodal therapeutic effect of tumors. This study provided a novel CR organic molecule-based theranostic nanoplatform that can be used to treat tumors via calcium overload therapy synergetic PTT at safe temperatures, which has promising potential for the future clinical cancer treatment.

Special Issue: "Soft Magnetic Materials and Their Applications".

Soft magnetic materials normally show no magnetic properties outside of a magnetic field but can be easily magnetized and demagnetized within magnetic fields [...].

Low Core Losses of Fe-Based Soft Magnetic Composites with an Zn-O-Si Insulating Layer Obtained by Coupling Synergistic Photodecomposition.

The major method used to reduce the magnetic loss of soft magnetic composites (SMCs) is to coat the magnetic powder with an insulating layer, but the permeability is usually sacrificed in the process. In order to achieve a better balance between low losses and high permeability, a novel photodecomposition method was used in this study to create a ZnO insulating layer. The effect of the concentration of diethyl zinc on the formation of a ZnO insulating film by photodecomposition was studied. The ZnO film was best formed with a diethyl zinc n-hexane solution at a concentration of around 0.40 mol/L. Combined with conventional coupling treatment processes, a thin and dense insulating layer was coated on the surface of iron powder in situ. Treating the iron powder before coating by photodecomposition led to a synergistic effect, significantly reduced core loss, and the effective permeability only decreased slightly. An iron-based soft magnetic composite with a loss value of 124 kW/m3 and an effective permeability of 107 was obtained at the frequency of 100 kHz and a magnetic field intensity of 20 mT.

Injection Molding and Sintering of ZrO2 Ceramic Powder Modified by a Zirconate Coupling Agent.

Ceramic injection molding is a near-net shape-processing technique, producing ceramic components with low tooling costs and complex shapes. In this paper, ZrO2 ceramics with high loading content in the green part were prepared by powder modification using zirconate coupling agent, injection molding and sintering, which benefited decreasing the usage of binders and deformation of ceramics. The rheological characteristics of feedstocks, densities, microstructures and mechanical properties of green and sintered parts with the different coupling media and sintering temperatures were studied. The results showed that the addition of a zirconate coupling agent with ethanol medium obviously increased the flowability of feedstocks and benefited achieving the green parts with high powder loading (86.5 wt.%) and bending strength (12.9 MPa) and the final unbroken ceramics. In addition, the sintering temperatures from 1500-1575 °C had no significant effects on the density, hardness, and surface morphology of the ceramic samples. However, the bending strength increased and some large grains with transgranular fracture occurred on the fractural surface at the sintering temperature of 1575 °C.

Hypoxia-Overcoming Breast-Conserving Treatment by Magnetothermodynamic Implant for a Localized Free-Radical Burst Combined with Hyperthermia.

For the purpose of improving the quality of life and minimizing the psychological morbidity of a mastectomy, breast-conserving treatment (BCT) has become the more preferable choice in breast cancer patients. Meanwhile, tumor hypoxia has been increasingly recognized as a major deleterious factor in cancer therapies. In the current study, a novel, effective, and noninvasive magnetothermodynamic strategy based on an oxygen-independent free-radical burst for hypoxia-overcoming BCT is proposed. Radical precursor (AIPH) and iron oxide nanoparticles (IONPs) are coincorporated within the alginate (ALG) hydrogel, which is formed in situ within the tumor tissue by leveraging the cross-linking effect induced by the local physiological Ca2+ with ALG solution. Inductive heating is mediated by IONPs under AMF exposure, and consequently, regardless of the tumor hypoxia condition, a local free-radical burst is achieved by thermal decomposition of AIPH via AMF responsivity. The combination of magnetic hyperthermia and oxygen-irrelevant free-radical production effectively enhances the in vitro cytotoxic effect and also remarkably inhibits tumor proliferation. This study provides a valuable protocol for an hypoxia-overcoming strategy and also an alternative formulation candidate for noninvasive BCT.

Carbothermal Reduction Synthesis of Aluminum Nitride from Al(OH)3/C/PVB Slurries Prepared by Three-Roll Mixing.

Polyvinyl butyral (PVB) was used in the Al(OH)3/carbon black/ethanol slurries by the three-roll mixing to prepare AlN powder using the carbothermal reduction-nitridation (CRN) process in the experiments. The effects of PVB addition on the synthesis of AlN powder were studied by viscosity, tap density, XRD, SEM and TG measurements. The results showed that the PVB layer covering on the surface of Al(OH)3 particles reduced the viscosity of Al(OH)3/carbon/ethanol slurry and increased the dispersion homogeneity of Al(OH)3/carbon raw powder. The tap densities of the Al(OH)3/carbon mixtures after three-roll milling could be increased with the increase in PVB addition. In the CRN process, most of the PVB covering Al(OH)3 particles evaporated and supplied the passage for nitrogen removal to the particles. Based on the experimental data, the role of PVB on the mixing and CRN process was discussed.

H2O2-independent chemodynamic therapy initiated from magnetic iron carbide nanoparticle-assisted artemisinin synergy.

Chemodynamic therapy (CDT) is a booming technology that utilizes Fenton reagents to kill tumor cells by transforming intracellular H2O2 into reactive oxygen species (ROS), but insufficient endogenous H2O2 makes it difficult to attain satisfactory antitumor results. In this article, a H2O2-free CDT technique with tumor-specificity is developed by using pH-sensitive magnetic iron carbide nanoparticles (PEG/Fe2C@Fe3O4 NPs) to trigger artemisinin (ART) to in situ form ROS. ART-loaded PEG/Fe2C@Fe3O4 NPs are fabricated for the enormous release of Fe2+ ions induced by the acidic conditions of the tumor microenvironment after magnetic-assisted tumor enrichment, which results in the rapid degradation of the PEG/Fe2C@Fe3O4 NPs and release of ART once endocytosed into tumor cells. In situ catalysis reaction between the co-released Fe2+ ions and ART generates toxic ROS and then induces apoptosis of tumor cells. Both in vitro and in vivo experiments demonstrate that the efficient Fe-enhanced and tumor-specific CDT efficacy for effective tumor inhibition based on ROS generation. This work provides a new direction to improve CDT efficacy based on H2O2-independent ROS generation.

Dihydroartemisinin loaded layered double hydroxide nanocomposites for tumor specific photothermal-chemodynamic therapy.

With the inspiration to develop new cancer nanotherapeutics by repurposing old drugs, in the current study, a novel two dimensional nanomedicine namely Mn doped, dihydroartemisinin (DHA) loaded layered double hydroxide (MnMgFe-LDH/DHA) with peroxide self-supplying properties for enhanced photothermal-chemodynamic therapy was proposed. Such nanostructures could be synthesized by a simple coprecipitation method, and the as-prepared MnMgFe-LDH/DHA exhibits excellent photothermal properties with a photothermal conversion efficiency up to 10.7%. Besides, the in situ reaction between the released DHA and Fe2+/Mn2+ produced by the degradation of LDH can lead to a burst of intracellular reactive oxygen species (ROS) by Fenton-like reactions. Furthermore, the in vivo experiments demonstrate that MnMgFe-LDH/DHA exhibits a remarkable chemodynamic/photothermal therapy (CDT/PTT) synergistic effect on tumor treatment with negligible damage to normal tissues. Finally, this research provides a smart strategy to construct a DHA repurposing nanomedicine for tumor specific treatment.

Magnetic Reactive Oxygen Species Nanoreactor for Switchable Magnetic Resonance Imaging Guided Cancer Therapy Based on pH-Sensitive Fe5C2@Fe3O4 Nanoparticles.

Reactive oxygen species (ROS) are crucial molecules in cancer therapy. Unfortunately, the therapeutic efficiency of ROS is unsatisfactory in clinic, primarily due to their rigorous production conditions. By taking advantage of the intrinsic acidity and overproduction of H2O2 in the tumor environment, we have reported an ROS nanoreactor based on core-shell-structured iron carbide (Fe5C2@Fe3O4) nanoparticles (NPs) through the catalysis of the Fenton reaction. These NPs are able to release ferrous ions in acidic environments to disproportionate H2O2 into •OH radicals, which effectively inhibits the proliferation of tumor cells both in vitro and in vivo. The high magnetization of Fe5C2@Fe3O4 NPs is favorable for both magnetic targeting and T2-weighted magnetic resonance imaging (MRI). Ionization of these NPs simultaneously decreases the T2 signal and enhances the T1 signal in MRI, and this T2/T1 switching process provides the visualization of ferrous ions release and ROS generation for the supervision of tumor curing. These Fe5C2@Fe3O4 NPs show great potential in endogenous environment-excited cancer therapy with high efficiency and tumor specificity and can be guided further by MRI.

Iron carbide nanoparticles: an innovative nanoplatform for biomedical applications.

Iron carbide nanoparticles (ICNPs) are nano-intermetallic compounds that consist of iron and carbon. Benefiting from the magnetic and chemical activity of iron, and/or mechanical strength and chemical inertness of carbon, they have been widely applied in energetic and biomedical-related fields. Particularly in biomedicine, ICNPs have shown high colloidal stability and good performance in magnetic-dependent diagnosis and therapies such as magnetic resonance imaging (MRI) and magnetic hyperthermia (MH), due to their high magnetization and moderate coercivity. The carbon content protects ICNPs from oxidation and corrosion (ion release), which prolongs their life time and reduces their toxicity in physiological environments, and endows nanoparticles (NPs) with high performance in carbon-relevant theranostics as well. On this basis, ICNPs have great promise in multi-modal imaging or imaging-guided tumor-selective therapy to realize precise diagnoses with mild side effects. This paper aims to cover the state of the art applications of ICNPs in biomedicine, primarily including MRI, MH, magnetic targeting (MT), magnetic separation (MS), photothermal therapy (PTT) and photoacoustic tomography (PAT). The biocompatibility of ICNPs is also addressed.