Nanoagents Based on Poly(ethylene glycol)‐b‐Poly(l‐thyroxine) Block Copolypeptide for Enhanced Dual‐Modality Imaging and Targeted Tumor Radiotherapy

Future healthcare requires development of novel theranostic agents that are capable of not only enhancing diagnosis and monitoring therapeutic responses but also augmenting therapeutic outcomes. Here, a versatile and stable nanoagent is reported based on poly(ethylene glycol)‐b‐poly(l ‐thyroxine) (PEG‐PThy) block copolypeptide for enhanced single photon emission computed tomography/computed tomography (SPECT/CT) dual‐modality imaging and targeted tumor radiotherapy in vivo. PEG‐PThy acquired by polymerization of l ‐thyroxine‐N‐carboxyanhydride (Thy‐NCA) displays a controlled M_n, high iodine content of ≈49.2 wt%, and can spontaneously form 65 nm‐sized nanoparticles (PThyN). In contrast to clinically used contrast agents like iohexol and iodixanol, PThyN reveals iso‐osmolality, low viscosity, and long circulation time. While PThyN exhibits comparable in vitro CT attenuation efficacy to iohexol, it greatly enhances in vivo CT imaging of vascular systems and soft tissues. PThyN allows for surface decoration with the cRGD peptide achieving enhanced CT imaging of subcutaneous B16F10 melanoma and orthotopic A549 lung tumor. Taking advantages of a facile iodine exchange reaction, ¹²⁵I‐labeled PThyN enables SPECT/CT imaging of tumors and monitoring of PThyN biodistribution in vivo. Besides, ¹³¹I‐labeled and cRGD‐functionalized PThyN displays remarkable growth inhibition of the B16F10 tumor in mice (tumor inhibition rate > 89%). These poly(l ‐thyroxine) nanoparticles provide a unique and versatile theranostic platform for varying diseases.     

An X-ray computed tomography imaging agent based on long-circulating bismuth sulphide nanoparticles

Nanomaterials have become increasingly important in the development of new molecular probes for in vivo imaging, both experimentally and clinically. Nanoparticulate imaging probes have included semiconductor quantum dots, magnetic and magnetofluorescent nanoparticles, gold nanoparticles and nanoshells, among others. However, the use of nanomaterials for one of the most common imaging techniques, computed tomography (CT), has remained unexplored. Current CT contrast agents are based on small iodinated molecules. They are effective in absorbing X-rays, but non-specific distribution and rapid pharmacokinetics have rather limited their microvascular and targeting performance. Here we propose the use of a polymer-coated Bi(2)S(3) nanoparticle preparation as an injectable CT imaging agent. This preparation demonstrates excellent stability at high concentrations (0.25 M Bi(3+)), high X-ray absorption (fivefold better than iodine), very long circulation times (>2 h) in vivo and an efficacy/safety profile comparable to or better than iodinated imaging agents. We show the utility of these polymer-coated Bi(2)S(3) nanoparticles for enhanced in vivo imaging of the vasculature, the liver and lymph nodes in mice. These nanoparticles and their bioconjugates are expected to become an important adjunct to in vivo imaging of molecular targets and pathological conditions.     

915 nm Light‐Triggered Photodynamic Therapy and MR/CT Dual‐Modal Imaging of Tumor Based on the Nonstoichiometric Na0.52YbF3.52:Er Upconversion Nanoprobes

Lanthanide (Ln³⁺)‐doped upconversion nanoparticles (UCNPs) as a new generation of multimodal bioprobes have attracted great interest for theranostic purpose. Herein, red emitting nonstoichiometric Na_0.52YbF_3.52:Er UCNPs of high luminescence intensity and color purity are synthesized via a facile solvothermal method. The red UC emission from the present nanophosphors is three times more intense than the well‐known green emission from the ≈30 nm sized hexagonal‐phase NaYF₄:Yb,Er UCNPs. By utilizing Na_0.52YbF_3.52:Er@SrF₂ UCNPs as multifunctional nanoplatforms, highly efficient in vitro and in vivo 915 nm light‐triggered photodynamic therapies are realized for the first time, with dramatically diminished overheating yet similar therapeutic effects in comparison to those triggered by 980 nm light. Moreover, by virtue of the high transverse relaxivity (r ₂) and the strong X‐ray attenuation ability of Yb³⁺ ions, these UCNPs also demonstrate good performances as contrast agents for high contrast magnetic resonance and X‐ray computed tomography dual‐modal imaging. Our research shows the great potential of the red emitting Na_0.52YbF_3.52:Er UCNPs for multimodal imaging‐guided photodynamic therapy of tumors.     

Multimodal Precision Imaging of Pulmonary Nanoparticle Delivery in Mice: Dynamics of Application,Spatial Distribution,and Dosimetry

Targeted delivery of nanomedicine/nanoparticles (NM/NPs) to the site of disease (e.g., the tumor or lung injury) is of vital importance for improved therapeutic efficacy. Multimodal imaging platforms provide powerful tools for monitoring delivery and tissue distribution of drugs and NM/NPs. This study introduces a preclinical imaging platform combining X‐ray (two modes) and fluorescence imaging (three modes) techniques for time‐resolved in vivo and spatially resolved ex vivo visualization of mouse lungs during pulmonary NP delivery. Liquid mixtures of iodine (contrast agent for X‐ray) and/or (nano)particles (X‐ray absorbing and/or fluorescent) are delivered to different regions of the lung via intratracheal instillation, nasal aspiration, and ventilator‐assisted aerosol inhalation. It is demonstrated that in vivo propagation‐based phase‐contrast X‐ray imaging elucidates the dynamic process of pulmonary NP delivery, while ex vivo fluorescence imaging (e.g., tissue‐cleared light sheet fluorescence microscopy) reveals the quantitative 3D drug/particle distribution throughout the entire lung with cellular resolution. The novel and complementary information from this imaging platform unveils the dynamics and mechanisms of pulmonary NM/NP delivery and deposition for each of the delivery routes, which provides guidance on optimizing pulmonary delivery techniques and novel‐designed NM for targeting and efficacy.     

“The Easier the Better” Preparation of Efficient Photocatalysts—Metastable Poly(heptazine imide) Salts

Cost‐efficient, visible‐light‐driven hydrogen production from water is an attractive potential source of clean, sustainable fuel. Here, it is shown that thermal solid state reactions of traditional carbon nitride precursors (cyanamide, melamine) with NaCl, KCl, or CsCl are a cheap and straightforward way to prepare poly(heptazine imide) alkali metal salts, whose thermodynamic stability decreases upon the increase of the metal atom size. The chemical structure of the prepared salts is confirmed by the results of X‐ray photoelectron and infrared spectroscopies, powder X‐ray diffraction and electron microscopy studies, and, in the case of sodium poly(heptazine imide), additionally by atomic pair distribution function analysis and 2D powder X‐ray diffraction pattern simulations. In contrast, reactions with LiCl yield thermodynamically stable poly(triazine imides). Owing to the metastability and high structural order, the obtained heptazine imide salts are found to be highly active photocatalysts in Rhodamine B and 4‐chlorophenol degradation, and Pt‐assisted sacrificial water reduction reactions under visible light irradiation. The measured hydrogen evolution rates are up to four times higher than those provided by a benchmark photocatalyst, mesoporous graphitic carbon nitride. Moreover, the products are able to photocatalytically reduce water with considerable reaction rates, even when glycerol is used as a sacrificial hole scavenger.     

Breaking the Depth Dependence by Nanotechnology‐Enhanced X‐Ray‐Excited Deep Cancer Theranostics

The advancements in nanotechnology have created multifunctional nanomaterials aimed at enhancing diagnostic accuracy and treatment efficacy for cancer. However, the ability to target deep‐seated tumors remains one of the most critical challenges for certain nanomedicine applications. To this end, X‐ray‐excited theranostic techniques provide a means of overcoming the limits of light penetration and tissue attenuation. Herein, a comprehensive overview of the recent advances in nanotechnology‐enhanced X‐ray‐excited imaging and therapeutic methodologies is presented, with an emphasis on the design of multifunctional nanomaterials for contrast‐enhanced computed tomography (CT) imaging, X‐ray‐excited optical luminescence (XEOL) imaging, and X‐ray‐excited multimodal synchronous/synergistic therapy. The latter is based on the concurrent use of radiotherapy with chemotherapy, gas therapy, photodynamic therapy, or immunotherapy. Moreover, the featured biomedical applications of X‐ray‐excited deep theranostics are discussed to highlight the advantages of X‐ray in high‐sensitivity detection and efficient elimination of malignant tumors. Finally, key issues and technical challenges associated with this deep theranostic technology are identified, with the intention of advancing its translation into the clinic.     

Synthesis of BSA‐Coated BiOI@Bi2S3 Semiconductor Heterojunction Nanoparticles and Their Applications for Radio/Photodynamic/Photothermal Synergistic Therapy of Tumor

Developing an effective theranostic nanoplatform remains a great challenge for cancer diagnosis and treatment. Here, BiOI@Bi₂S₃@BSA (bovine serum albumin) semiconductor heterojunction nanoparticles (SHNPs) for triple‐combination radio/photodynamic/photothermal cancer therapy and multimodal computed tomography/photoacoustic (CT/PA) bioimaging are reported. On the one hand, SHNPs possess strong X‐ray attenuation capability since they contain high‐Z elements, and thus they are anticipated to be a very competent candidate as radio‐sensitizing materials for radiotherapy enhancement. On the other hand, as a semiconductor, the as‐prepared SHNPs offer an extra approach for reactive oxygen species generation based on electron–hole pair under the irradiation of X‐ray through the photodynamic therapy process. This X‐ray excited photodynamic therapy obviously has better penetration depth in bio‐tissue. What's more, the SHNPs also possess well photothermal conversion efficiency for photothermal therapy, because Bi₂S₃ is a thin band semiconductor with strong near‐infrared absorption that can cause local overheat. In vivo tumor ablation studies show that synergistic radio/photodynamic/photothermal therapy achieves more significant therapeutic effect than any single treatment. In addition, with the strong X‐ray attenuation and high near‐infrared absorption, the as‐obtained SHNPs can also be applied as a multimodal contrast agent in CT/PA imaging.     

Iodine‐Rich Semiconducting Polymer Nanoparticles for CT/Fluorescence Dual‐Modal Imaging‐Guided Enhanced Photodynamic Therapy

Photodynamic therapy (PDT) is a promising technique for cancer therapy, providing good therapeutic efficacy with minimized side effect. However, the lack of oxygen supply in the hypoxic tumor site obviously restricts the generation of singlet oxygen (¹O₂), thus limiting the efficacy of PDT. So far, the strategies to improve PDT efficacy usually rely on complicated nanosystems, which require sophisticated design or complex synthetic procedure. Herein, iodine‐rich semiconducting polymer nanoparticles (SPN‐I) for enhanced PDT, using iodine‐induced intermolecular heavy‐atom effect to elevate the ¹O₂ generation, are designed and prepared. The nanoparticles are composed of a near‐infrared (NIR) absorbing semiconducting polymer (PCPDTBT) serving as the photosensitizer and source of fluorescence signal, and an iodine‐grafted amphiphilic diblock copolymer (PEG‐PHEMA‐I) serving as the ¹O₂ generation enhancer and nanocarrier. Compared with SPN composed of PEG‐b‐PPG‐b‐PEG and PCPDTBT (SPN‐P), SPN‐I can enhance the ¹O₂ generation by 1.5‐fold. In addition, SPN‐I have high X‐ray attenuation coefficient because of the high density of iodine in PEG‐PHEMA‐I, providing SPN‐I the ability of use with computed tomography (CT) and fluorescence dual‐modal imaging. The study thus provides a simple nanotheranostic platform composed of two components for efficient CT/fluorescence dual‐modal imaging‐guided enhanced PDT.     

Shedding Light on Metal‐Based Nanoparticles in Zebrafish by Computed Tomography with Micrometer Resolution

Metal‐based nanoparticles are clinically used for diagnostic and therapeutic applications. After parenteral administration, they will distribute throughout different organs. Quantification of their distribution within tissues in the 3D space, however, remains a challenge owing to the small particle diameter. In this study, synchrotron radiation‐based hard X‐ray tomography (SRμCT) in absorption and phase contrast modes is evaluated for the localization of superparamagnetic iron oxide nanoparticles (SPIONs) in soft tissues based on their electron density and X‐ray attenuation. Biodistribution of SPIONs is studied using zebrafish embryos as a vertebrate screening model. This label‐free approach gives rise to an isotropic, 3D, direct space visualization of the entire 2.5 mm‐long animal with a spatial resolution of around 2 µm. High resolution image stacks are available on a dedicated internet page ( http://zebrafish.pharma-te.ch ). X‐ray tomography is combined with physico‐chemical characterization and cellular uptake studies to confirm the safety and effectiveness of protective SPION coatings. It is demonstrated that SRμCT provides unprecedented insights into the zebrafish embryo anatomy and tissue distribution of label‐free metal oxide nanoparticles.     

Synchrotron‐Based Micro‐CT and Refraction‐Enhanced Micro‐CT for Non‐Destructive Materials Characterisation

X‐ray computed tomography is an important tool for non‐destructively evaluating the 3‐D microstructure of modern materials. To resolve material structures in the micrometer range and below, high brilliance synchrotron radiation has to be used. The Federal Institute for Materials Research and Testing (BAM) has built up an imaging setup for micro‐tomography and ‐radiography (BAMline) at the Berliner storage ring for synchrotron radiation (BESSY). In computed tomography, the contrast at interfaces within heterogeneous materials can be strongly amplified by effects related to X‐ray refraction. Such effects are especially useful for materials of low absorption or mixed phases showing similar X‐ray absorption properties that produce low contrast. The technique is based on ultra‐small‐angle scattering by microstructural elements causing phase‐related effects, such as refraction and total reflection. The extraordinary contrast of inner surfaces is far beyond absorption effects. Crack orientation and fibre/matrix debonding in plastics, polymers, ceramics and metal‐matrix‐composites after cyclic loading and hydro‐thermal aging can be visualized. In most cases, the investigated inner surface and interface structures correlate to mechanical properties. The technique is an alternative to other attempts on raising the spatial resolution of CT machines.     

Plastic Deformation of a Nano‐Precipitate Strengthened Ni‐Base Alloy Investigated by Complementary In Situ Neutron Diffraction Measurements and Molecular‐Dynamics Simulations

In situ neutron‐diffraction experiments at the spallation neutron source, simultaneously illuminating the diffraction of the matrix and the strengthening nano precipitates, allow the determination of their plastic deformation. An irreversible neutron‐diffraction‐profile evolution of the nano precipitates is observed. However, there is no conclusive trend of the nano‐precipitate peak‐width evolution subjected to the greater stress levels. Hence, in the present work, molecular‐dynamics simulations are applied to reveal the deformation mechanisms of the nano precipitate and its interaction with the surrounding matrix. The microstructure size, dislocation content, and structural parameters of the nano precipitates, quantified by X‐ray, transmission electron microscopy, and small‐angle neutron scattering, are used as the simulation input and reference. The simulation results show that there are two competing deformation mechanisms, which lead to the fluctuation of the nano‐precipitate‐diffraction widths, occurring during the higher plastic deformation stages.     

Small is Smarter: Nano MRI Contrast Agents – Advantages and Recent Achievements

Many challenges for advanced sensitive and noninvasive clinical diagnostic imaging remain unmatched. In particular, the great potential of magnetic nano‐probes is intensively discussed to further improve the performance of magnetic resonance imaging (MRI), especially for cancer diagnosis. Based on recent achievements, here the concepts of magnetic nanoparticle‐based MRI contrast agents and tumor‐specific imaging probes are critically summarized. Advances in their synthesis, biocompatible chemical and biofunctional surface modifications, and current strategies for further developing them into multimodality imaging probes are discussed. In addition, how engineered versus unintended surface coatings such as protein coronas affect the biocompatibility and performance of MRI nano‐probes is also considered. To stimulate progress in the field, future strategies and relevant challenges that still need to be resolved in the field conclude this review.     

Reinforcement in Al Matrix Composites: A Review of Strengthening Behavior of Nano‐Sized Particles

Aluminum matrix composites (AMCs) reinforced with the nano‐sized particles are very important materials for the applications in industrial fields. These aluminum matrix composites consist of an aluminum matrix and nano‐sized particles, which own very different physical and mechanical properties from those of the matrix. Nano‐sized particles show a more obvious strengthening effect on the matrix than the micro‐sized particles do, because of the high specific surface area which is positive for the pinning effect during the deformation process. Thus, the nano‐sized particle‐reinforced AMCs usually exhibit a good ductility. The main issues of the fabrication methods are the low wettability between the nano‐sized particles and the molten aluminum alloys, which is fatal to the conventional casting methods, and the agglomeration of nano‐sized particles which happened easier than the larger particles. Several alternative processes have been presented in literature for the production of the nano‐sized particle‐reinforced aluminum composites. This paper is aimed at reviewing the feasible manufacturing techniques used for the fabrication of nano‐sized particle‐reinforced aluminum composites. More importantly, the strengthening mechanisms and models which are responsible for the improvement of mechanical properties of the nano‐sized particle‐reinforced aluminum composites have been reviewed.

     

Boron Dipyrromethene Nano‐Photosensitizers for Anticancer Phototherapies

As traditional phototherapy agents, boron dipyrromethene (BODIPY) photosensitizers have attracted increasing attention due to their high molar extinction coefficients, high phototherapy efficacy, and excellent photostability. After being formed into nanostructures, BODIPY‐containing nano‐photosensitizers show enhanced water solubility and biocompatibility as well as efficient tumor accumulation compared to BODIPY molecules. Hence, BODIPY nano‐photosensitizers demonstrate a promising potential for fighting cancer. This review contains three sections, classifying photodynamic therapy (PDT), photothermal therapy (PTT), and the combination of PDT and PTT based on BODIPY nano‐photosensitizers. It summarizes various BODIPY nano‐photosensitizers, which are prepared via different approaches including molecular precipitation, supramolecular interactions, and polymer encapsulation. In each section, the design strategies and working principles of these BODIPY nano‐photosensitizers are highlighted. In addition, the detailed in vitro and in vivo applications of these recently developed nano‐photosensitizers are discussed together with future challenges in this field, highlighting the potential of these promising nanoagents for new tumor phototherapies.     

Ordered Arrays of Nanostructures and Applications in High‐Efficient Nano‐Generators

Large‐scale ordered nanostructure arrays on substrates, including nanowires, nanotubes, nanodots, and nano‐holes, can be fabricated using template fabrication processes. The controllable structural parameters and properties of the ordered nanostructure arrays make them quite suitable to be used in many device‐related application areas. It is shown that large‐scale nanowire arrays are good candidates for the realization of a nano‐generator based on the piezoelectric effect of ZnO nanowires. The mechanism of a proposed high‐efficient nano‐generator based on an assembled nanowire/nanohole embedded structure shows high application potentials for biological and nanometer‐sized devices.     

Magneto‐Plasmonic Au‐Fe Alloy Nanoparticles Designed for Multimodal SERS‐MRI‐CT Imaging

Diagnostic approaches based on multimodal imaging are needed for accurate selection of the therapeutic regimens in several diseases, although the dose of administered contrast drugs must be reduced to minimize side effects. Therefore, large efforts are deployed in the development of multimodal contrast agents (MCAs) that permit the complementary visualization of the same diseased area with different sensitivity and different spatial resolution by applying multiple diagnostic techniques. Ideally, MCAs should also allow imaging of diseased tissues with high spatial resolution during surgical interventions. Here a new system based on multifunctional Au‐Fe alloy nanoparticles designed to satisfy the main requirements of an ideal MCA is reported and their biocompatibility and imaging capability are described. The MCAs show easy and versatile surface conjugation with thiolated molecules, magnetic resonance imaging (MRI) and computed X‐ray tomography (CT) signals for anatomical and physiological information (i.e., diagnostic and prognostic imaging), large Raman signals amplified by surface enhanced Raman scattering (SERS) for high sensitivity and high resolution intrasurgical imaging, biocompatibility, exploitability for in vivo use and capability of selective accumulation in tumors by enhanced permeability and retention effect. Taken together, these results show that Au‐Fe nanoalloys are excellent candidates as multimodal MRI‐CT‐SERS imaging agents.     

Inorganic Nanoparticles for MRI Contrast Agents

Various inorganic nanoparticles have been used as magnetic resonance imaging (MRI) contrast agents due to their unique properties, such as large surface area and efficient contrasting effect. Since the first use of superparamagnetic iron oxide (SPIO) as a liver contrast agent, nanoparticulate MRI contrast agents have attracted a lot of attention. Magnetic iron oxide nanoparticles have been extensively used as MRI contrast agents due to their ability to shorten T2* relaxation times in the liver, spleen, and bone marrow. More recently, uniform ferrite nanoparticles with high crystallinity have been successfully employed as new T2 MRI contrast agents with improved relaxation properties. Iron oxide nanoparticles functionalized with targeting agents have been used for targeted imaging via the site‐specific accumulation of nanoparticles at the targets of interest. Recently, extensive research has been conducted to develop nanoparticle‐based T1 contrast agents to overcome the drawbacks of iron oxide nanoparticle‐based negative T2 contrast agents. In this report, we summarize the recent progress in inorganic nanoparticle‐based MRI contrast agents.     

Corrosion‐Activated Chemotherapeutic Function of Nanoparticulate Platinum as a Cisplatin Resistance‐Overcoming Prodrug with Limited Autophagy Induction

Despite nanoparticulate platinum (nano‐Pt) has been validated to be acting as a platinum‐based prodrug for anticancer therapy, the key factor in controlling its cytotoxicity remains to be clarified. In this study, it is found that the corrosion susceptibility of nano‐Pt can be triggered by inducing the oxidization of superficial Pt atoms, which can kill both cisplatin‐sensitive/resistance cancer cells. Direct evidence in the oxidization of superficial Pt atoms is validated to observe the formation of platinum oxides by X‐ray absorption spectroscopy. The cytotoxicity is originated from the dissolution of nano‐Pt followed by the release of highly toxic Pt ions during the corrosion process. Additionally, the limiting autophagy induction by nano‐Pt might prevent cancer cells from acquiring autophagy‐related drug resistance. With such advantages, the possibility of further autophagy‐related drug resistance could be substantially reduced or even eliminated in cancer cells treated with nano‐Pt. Moreover, nano‐Pt is demonstrated to kill cisplatin‐resistant cancer cells not only by inducing apoptosis but also by inducing necrosis for pro‐inflammatory/inflammatory responses. Thus, nano‐Pt treatment might bring additional therapeutic benefits by regulating immunological responses in tumor microenvironment. These findings support the idea that utilizing nano‐Pt for its cytotoxic effects might potentially benefit patients with cisplatin resistance in clinical chemotherapy.     

Anti‐Biofouling Polymer‐Decorated Lutetium‐Based Nanoparticulate Contrast Agents for In Vivo High‐Resolution Trimodal Imaging

Nanomaterials have gained considerable attention and interest in the development of novel and high‐resolution contrast agents for medical diagnosis and prognosis in clinic. A classical urea‐based homogeneous precipitation route that combines the merits of in situ thermal decomposition and surface modification is introduced to construct polyethylene glycol molecule (PEG)‐decorated hybrid lutetium oxide nanoparticles (PEG–UCNPs). By utilizing the admirable optical and magnetic properties of the yielded PEG–UCNPs, in vivo up‐conversion luminescence and T₁‐enhanced magnetic resonance imaging of small animals are conducted, revealing obvious signals after subcutaneous and intravenous injection, respectively. Due to the strong X‐ray absorption and high atomic number of lanthanide elements, X‐ray computed‐tomography imaging based on PEG–UCNPs is then designed and carried out, achieving excellent imaging outcome in animal experiments. This is the first example of the usage of hybrid lutetium oxide nanoparticles as effective nanoprobes. Furthermore, biodistribution, clearance route, as well as long‐term toxicity are investigated in detail after intravenous injection in a murine model, indicating the overall safety of PEG–UCNPs. Compared with previous lanthanide fluorides, our nanoprobes exhibit more advantages, such as facile construction process and nearly total excretion from the animal body within a month. Taken together, these results promise the use of PEG–UCNPs as a safe and efficient nanoparticulate contrast agent for potential application in multimodal imaging.     

High‐Energy X‐Ray Diffraction Study of the Inhomogeneous Zr43Cu43Al7Ag7 Bulk‐Metallic Glasses

In the present work, the microscopic structure of an as‐cast Zr₄₃Cu₄₃Al₇Ag₇ bulkmetallic glass (BMG) had been investigated in detail. The structure analyses are performed using the laboratory X‐ray diffraction (XRD), high‐energy synchrotron X‐ray diffraction, and transmission‐electron microscopy (TEM). The results from different techniques are compared and discussed. The specimen shows a typical amorphous hallo using the conventional laboratory XRD. However, tiny crystalline particles, roughly ≈10 nm in size, are found in the sample by the high‐energy XRD as well as the TEM. The standard laboratory XRD measurement is not adequate to differentiate amorphous from a nano‐composite phase. The high‐energy XRD method is an essential technique to determine the glassy nature of a BMG.