Peroxidase-Mimicking Ir-Te Nanorods for Photoconversion-Combined Multimodal Cancer Therapy.

Owing to multiple physicochemical properties, the combination of hybrid elemental compositions of nanoparticles can be widely utilized for a variety of applications. To combine pristine tellurium nanorods, which act as a sacrificing template, with another element, iridium-tellurium nanorods (IrTeNRs) were synthesized via the galvanic replacement technique. Owing to the coexistence of iridium and tellurium, IrTeNRs exhibited unique properties, such as peroxidase-like activity and photoconversion. Additionally, the IrTeNRs demonstrated exceptional colloidal stability in complete media. Based on these properties, the IrTeNRs were applied to in vitro and in vivo cancer therapy, allowing for the possibility of multiple therapeutic methodologies. The enzymatic therapy was enabled by the peroxidase-like activity that generated reactive oxygen species, and the photoconversion under 473, 660 and 808 nm laser irradiation induced cancer cell apoptosis via photothermal and photodynamic therapy.

Rhodium-Tellurium Nanorod Synthesis Using Galvanic Replacement-Polyol Regrowth for Thermo-Dynamic Dual-Modal Cancer Phototherapy.

Rh is a noble metal introduced in bioapplications, including diagnosis and therapy, in addition to its consolidated utilization in organic catalysis and electrocatalysis. Herein, we designed the synthesis of highly crystalline Rh nanocrystal-decorated Rh-Te nanorods (RhTeNRs) through galvanic replacement of sacrificial Te nanorod (TeNR) templates and subsequent polyol regrowth. The obtained RhTeNRs showed excellent colloidal stability and efficient heat dissipation and photocatalytic activity under various laser irradiation wavelengths. Based on the confirmed biocompatibility, RhTeNRs were introduced into in vitro and in vivo cancer phototherapies. The results confirmed the selective physical death of cancer cells in the local area through laser irradiation. While chemotherapy does not guarantee successful treatment due to side effects and resistance, phototherapy using heat and reactive oxygen species generation of RhTeNRs induces physical death.

Precursor Heterogeneity Driven Mo-Te Nanoparticle Structural Diversification for Cancer Photo-Theranostics.

Chemical reactions between homogeneous precursors are typically used to synthesize monodisperse nanoparticles with well-controlled size and morphology. It is difficult to predict the evolved nanostructures when using two heterogeneous precursors. In this study, three types of Mo-Te nanoparticles shaped like leaves, spindles, and rice grains (denoted respectively as nanoleaf, nanospindle, and nanorice) were obtained from dextrose-mediated proton-coupled electron transfer reaction between the solid polyoxomolybdate (POM) and the ionic tellurite anion as precursors. All produced nanoparticles had excellent optical absorption in the ultraviolet(UV)-visible(Vis)-near-infrared(NIR) regions, with only slight deviations among them. After confirming nanoparticles' photothermal conversion and photocatalytic activity at multiple wavelengths, the Mo-Te nanorice was tested as a potential agent for cancer treatment due to its minimum toxicity, excellent colloidal stability, and intrinsic anticancer effect. Excellent treatment efficacy and clearance were confirmed in vitro and in vivo. Due to their photoacoustic imaging capability, the injection of pristine nanoparticles could also realize phototheranostics without using additional drugs, probes, or photosensitizers.

Fabrication of a surface-enhanced Raman spectroscopy-based analytical method consisting of multifunctional DNA three-way junction-conjugated porous gold nanoparticles and Au-Te nanoworm for C-reactive protein detection.

C-Reactive protein (CRP) is a biomarker of inflammatory responses and an index for assessing the risk of cardiovascular disease and estimating prognosis. In this study, we constructed a surface-enhanced Raman spectroscopy (SERS) biosensor composed of a multifunctional DNA three-way junction (DNA 3WJ), porous gold nanoplates (pAuNPs), and an Au-Te nanoworm structure for detection of CRP. The pAuNP and Au-Te nanostructures were synthesized by galvanic replacement reactions, and the morphology was confirmed by transmission electron microscopy, scanning electron microscopy, and dynamic light scattering (DLS). To generate the SERS signal, the Au-Te nanostructure was immobilized on an indium-tin oxide substrate, and the thiol-modified CRP aptamer was then self-assembled onto the modified substrate for CRP recognition. To amplify the SERS signal and identify the Raman tag, the multifunctional DNA 3WJ was conjugated with the pAuNPs, and each fragment of 3WJ was functionalized to biotin (pAuNP conjugation), methylene blue (Raman reporter), and CRP aptamer (target binding). The results were confirmed by gel electrophoresis. For conjugation between pAuNPs and DNA 3WJ, avidin was encapsulated in pAuNPs, and the conjugation structure was confirmed by DLS. The fabricated SERS biosensor showed detection limits of 2.23 pM in phosphate-buffered saline and 3.11 pM in diluted human serum. Overall, the proposed biosensor may have potential applications as a SERS biosensor platform.

Unveiling the Cationic Promotion Effect of H2O2 Electrosynthesis Activity of O-Doped Carbons.

H2O2 electrosynthesis is an emerging clean chemical technology, whose efficiency critically depends on the activity and selectivity of electrocatalysts for two-electron oxygen reduction reaction (2e- ORR). Here, we demonstrate that 2e- ORR activity of oxygen-doped carbons, which have been one of the most promising catalysts for this reaction, can be substantially influenced by the types and concentrations of cations in electrolytes. Heat-treated carbon comprising active oxygen functional groups exhibits cation-dependent 2e- ORR activity trends in alkaline media, following the order Cs+ > K+ > Li+. Importantly, an electrolyte with a high cation concentration (0.1 M KOH + 0.5 M KCl) afforded the highest 2e- ORR mass activity (250 ± 30 A gcat-1 at 0.70 V vs reversible hydrogen electrode) ever reported. We have established that the cation promotion effect correlates with cation-dependent electron-transfer kinetics, which regulates the rate-determining first electron transfer to O2.

Osmium-Tellurium Nanozymes for Pentamodal Combinatorial Cancer Therapy.

Although nanoparticles based on Group 8 elements such as Fe and Ru have been developed, not much is known about Os nanoparticles. However, Os-based nanostructures might have potential in various applications including biomedical fields. Therefore, in this study, we synthesized Os-Te nanorods (OsTeNRs) by solvothermal galvanic replacement with Te nanotemplates. We explored the nanozymatic activity of the synthesized OsTeNRs and found that they exhibited superior photothermal conversion and photocatalytic activity. Along with chemotherapy (regorafenib) and immunotherapy, the nanozymatic, photothermal, and photodynamic activities of OsTeNRs were harnessed to develop a pentamodal treatment for hepatocellular carcinoma (HCC); in vitro and in vivo studies demonstrated that the pentamodal therapy could alleviate hypoxia in HCC cells by generating oxygen and reduced unintended drug accumulation in organs. Moreover, bone-marrow toxicity due to regorafenib could be reduced as the drug was released in a sustained manner. Thus, OsTeNRs can be considered as suitable nanotemplates for combinatorial cancer therapy.

Fabrication of an electrochemical biosensor composed of multi-functional Ag ion intercalated DNA four-way junctions/rhodium nanoplate heterolayer on a micro-gap for C-reactive protein detection in human serum.

As inflammation plays a role in the pathogenesis of acute coronary syndromes, C-reactive protein (CRP) can be used as a biomarker. To detect CRP precisely, the authors prepared a CRP electrochemical biosensor consisting of an eight Ag ion-intercalated multifunctional DNA four-way junction (MF-DNA-4WJ) and a porous rhodium nanoparticle (pRhNP) heterolayer on a micro-gap electrode. To increase conductivity, we used eight Ag+ ion-inserted DNA four-way junctions through a C-C mismatch. Each DNA 4WJ was designed to have the CRP aptamer sequence, an anchoring region (thiol group), and two of four C-C mismatch regions at the end of the fragments. After an annealing step, the MF-DNA-4WJ assembly configuration and selective binding of CRP were confirmed through native TBM-PAGE (Tris-borate-magnesium chloride-polyacrylamide gel electrophoresis). The Au micro-gap electrode was fabricated to load 5 µl of the sample, and this was performed during eight experiments on one chip to establish the accuracy of the data. Then, pRhNPs were immobilized on a Au micro-gap electrode using cysteamine. To confirm the electrochemical properties, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were conducted. The durability of pRhNPs was confirmed through CV. To test the sensing performance of the prepared CRP biosensor, the limit of detection (LOD) and selectivity tests were conducted using EIS. The results indicated that charge transfer resistance (Rct) can be used efficiently to probe these interactions within the variable CRP concentration range, from 1 pM to 100 nM (0.23 ng L-1-23 µg L-1). The LOD of this sensor was 0.349 pM (0.08 ng L-1) (at S/N = 3). As a result of diluting the CRP to the same concentration range in a 20% human serum sample, the LOD was 3.55 fM (0.814 pg L-1) (at S/N = 3).

Intrinsic Peroxidase-Mimicking Ir Nanoplates for Nanozymatic Anticancer and Antibacterial Treatment.

The study of inorganic nanozymes to overcome the disadvantages of bio-enzymes, such as the requirement of optimized reaction conditions and lack of durability against environmental factors, is one of the most significant research topics at present. In this work, we comprehensively analyzed the intrinsic peroxidase-like activity of Ir-based nanoparticles, the biological and nanozymatic potentials of which have not yet been explored. These particles were synthesized by the galvanic replacement of Ag nanoplates with Ir. Through the confirmed peroxidase-like activity and hydrogen peroxide decomposition with free radical generation facilitated by these particles, the antibacterial and anticancer effects were successfully verified in vitro. The nanozyme-based therapeutic effect observed at concentrations at which these nanoparticles do not show cytotoxicity suggests that it is possible to achieve more precise and selective local treatment with these particles. The observed highly efficient peroxidase-like activity of these nanoparticles is attributed to the partially mixed composition of Ir-Ag-IrO2 formed through the galvanic replacement reaction in the synthetic process.

Fabrication of electrochemical biosensor composed of multi-functional DNA/rhodium nanoplate heterolayer for thyroxine detection in clinical sample.

Thyroxine (T4) contains four iodine atoms and is a major thyroid hormone synthesized in the thyroid gland. Abnormal levels of T4 in the body cause various endocrine diseases. The present study describes the fabrication of an electrochemical biosensor composed of a multi-functional DNA structure/rhodium nanoplates heterolayer for precise detection of T4 concentration. A DNA 3-way junction (3WJ) structure was designed as a multi-functional bioprobe to perform several functions (including target detection, electrochemical signal reporting, and immobilization) simultaneously. Binding between T4 and the T4 DNA aptamer was confirmed through enzyme-linked aptamer assays (ELAAs) and filtration experiments. The multi-functional DNA was immobilized on porous rhodium nanoplates (pRhNPs)-heterolayer modified Au micro-gap electrode. The pRhNPs provided an increment in the surface area and amplification of the electrochemical signal. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used to detect T4. Under optimal conditions, the limit of detection of T4 was found to be 10.33 pM. Furthermore, up to 11.41 pM of T4 could be detected in clinical samples. This study demonstrates the possibility of label-free detection of the T4 with multi-functional DNA/pRhNPs heterolayer that can be applied to small molecule detection platform in the near future.

Hydrothermal Galvanic-Replacement-Tethered Synthesis of Ir-Ag-IrO2 Nanoplates for Computed Tomography-Guided Multiwavelength Potent Thermodynamic Cancer Therapy.

Beyond the synthesis of typical nanocrystals, various breakthrough approaches have been developed to provide more useful structural features and functionalities. Among them, galvanic replacement, a structural transformation reaction accompanied by constituent element substitution, has been applied to various areas. However, the innovative improvement for galvanic replacement needs to be considered because of the limitation of applicable element pairs to maintain structural stability. To expand the boundary of galvanic-replacement-mediated synthesis, we have become interested in the Group 9 metallic element Ir, which is considered a fascinating element in the field of catalysis, but whose size and shape regulation has been conventionally regarded as difficult. To overcome the current limitations, we developed a hydrothermal galvanic-replacement-tethered synthetic route to prepare Ir-Ag-IrO2 nanoplates (IrNPs) with a transverse length of tens of nanometers and a rough surface morphology. A very interesting photoreactivity was observed from the prepared IrNPs, with Ag and IrO2 coexisting partially, which showed photothermal conversion and photocatalytic activity at different ratios against extinction wavelengths of 473, 660, and 808 nm. The present IrNP platform showed excellent photothermal conversion efficiency under near-infrared laser irradiation at 808 nm and also represented an effective cancer treatment in vitro and in vivo through a synergistic effect with reactive oxygen species (ROS) generation. In addition, computed tomography (CT) imaging contrast effects from Ir and IrO2 composition were also clearly observed.