Injectable biocompatible nanocomposites of Prussian blue nanoparticles and bacterial cellulose as a safe and effective photothermal cancer therapy.

Photothermal therapy (PTT) is a novel cancer treatment using a photoabsorber to cause hyperthermia to kill tumors by laser irradiation. Prussian blue nanoparticles (PB NPs) are considered as next-generation photothermal agents due to the facile synthesis and excellent absorption of near-infrared light. Although PB NPs demonstrate remarkable PTT capabilities, their clinical application is limited due to their systemic toxicity. Bacterial cellulose (BC) has been applied to various bio-applications based on its unique properties and biocompatibility. Herein, we design composites with PB NPs and BC as an injectable, highly biocompatible PTT agent (IBC-PB composites). Injectable bacterial cellulose (IBC) is produced through the trituration of BC, with PB NPs synthesized on the IBC surface to prepare IBC-PB composites. IBC-PB composites show in vitro and in vivo photothermal therapeutic effects similar to those of PB NPs but with significantly greater biocompatibility. Specifically, in vitro therapeutic index of IBC-PB composites is 26.5-fold higher than that of PB NPs. Furthermore, unlike PB NPs, IBC-PB composites exhibit no overt toxicity in mice as assessed by blood biochemical analysis and histological images. Hence, it is worth pursuing further research and development of IBC-PB composites as they hold promise as safe and efficacious PTT agents for clinical application.

In vitro magnetic hyperthermia properties of angle-shaped superparamagnetic iron oxide nanoparticles synthesized by a bromide-assisted polyol method.

Currently, research on superparamagnetic iron oxide nanoparticles (SPIONs) for magnetic hyperthermia applications is steadily increasing. In this work, SPIONs were synthesized by the bromide-assisted polyol method and angle-shaped SPIONs were successfully generated with the optimized concentration of bromide. The influence of bromide concentration on the shape of the generated SPIONs as well as the heating characteristics under an alternating magnetic field (AMF) was thoroughly investigated. At a concentration of 20 mg mL-1 of the angle-shaped SPIONs, the highest temperature curve up to 23 °C was observed under AMF with 140 Oe and 100 kHz for 10 min. With the biotoxicity assay, no significant cytotoxicity was observed in the normal fibroblast of HFB-141103 as well as tumor cells of U87MG and FSall treated with the angle-shaped SPIONs at a concentration below 100 µg mL-1. However, significantly decreased cellular viability was observed in tumor cells of U87MG and FSall treated with 100 µg mL-1 of the angle-shaped SPIONs under AMF with 140 Oe and 100 kHz. Based on these results, it is thought that the angle-shaped SPIONs synthesized by the bromide-assisted polyol method will provide highly efficient magnetic hyperthermia therapy for cancers under biologically safe AMF with 140 Oe and 100 kHz.

Phosphate Capture Enhancement Using Designed Iron Oxide-Based Nanostructures.

Phosphates in high concentrations are harmful pollutants for the environment, and new and cheap solutions are currently needed for phosphate removal from polluted liquid media. Iron oxide nanoparticles show a promising capacity for removing phosphates from polluted media and can be easily separated from polluted media under an external magnetic field. However, they have to display a high surface area allowing high removal pollutant capacity while preserving their magnetic properties. In that context, the reproducible synthesis of magnetic iron oxide raspberry-shaped nanostructures (RSNs) by a modified polyol solvothermal method has been optimized, and the conditions to dope the latter with cobalt, zinc, and aluminum to improve the phosphate adsorption have been determined. These RSNs consist of oriented aggregates of iron oxide nanocrystals, providing a very high saturation magnetization and a superparamagnetic behavior that favor colloidal stability. Finally, the adsorption of phosphates as a function of pH, time, and phosphate concentration has been studied. The undoped and especially aluminum-doped RSNs were demonstrated to be very effective phosphate adsorbents, and they can be extracted from the media by applying a magnet.

Induction of ferroptosis using functionalized iron-based nanoparticles for anti-cancer therapy.

Ferroptosis, a cell death pathway that is induced in response to iron, has recently attracted remarkable attention given its emerging therapeutic potential in cancer cells. The need for a promising modality to improve chemotherapy's efficacy through this pathway has been urgent in recent years, and this non-apoptotic cell death pathway accumulates reactive oxygen species (ROS) and is subsequently involved in lipid peroxidation. Here, we report cancer-targeting nanoparticles that possess highly efficient cancer-targeting ability and minimal systemic toxicity, thereby leading to ferroptosis. To overcome the limit of actual clinical application, which is the ultimate goal due to safety issues, we designed safe nanoparticles that can be applied clinically. Nanoparticles containing ferroptosis-dependent iron and FDA-approved hyaluronic acid (FHA NPs) are fabricated by controlling physicochemical properties, and the FHA NPs specifically induce ROS production and lipid peroxidation in cancer cells without affecting normal cells. The excellent in vivo anti-tumor therapeutic effect of FHA NPs was confirmed in the A549 tumor-bearing mice model, indicating that the induction of FHA NP-mediated cell death via the ferroptosis pathway could serve as a powerful platform in anticancer therapy. We believe that this newly proposed FHA NP-induced ferroptosis strategy is a promising system that offers the potential for efficient cancer treatment and provides insight into the safe design of nanomedicines for clinical applications.

Magnetic and near-infrared derived heating characteristics of dimercaptosuccinic acid coated uniform Fe@Fe3O4 core-shell nanoparticles.

Among the number of hyperthermia materials, magnetic nanoparticles have received much attention. In this work, we studied the heating characteristics of uniform Fe@Fe3O4 core-shell nanoparticle under near-infrared laser irradiation and external AC magnetic field applying. The Fe@Fe3O4 core-shell nanoparticles were prepared by thermal decomposition of iron pentacarbonyl and followed by controlled oxidation. The prepared uniform particles were further coated with dimercaptosuccinic acid to make them well dispersed in water. Near-infrared derived photothermal study of solutions containing a different concentration of the core-shell nanoparticles was made by using 808 nm laser Source. Additionally, magnetic hyperthermia ability of the Fe@Fe3O4 nanoparticle at 150 kHz and various oersted (140-180 Oe) condition was systemically characterized. The Fe@Fe3O4 nanoparticles which exhibited effective photo and magnetic hyperthermia are expected to be used in biomedical application.

Highly sensitive and selective visual detection of Cr(VI) ions based on etching of silver-coated gold nanorods.

We report a visual detection of Cr(VI) ions using silver-coated gold nanorods (AuNR@Ag) as sensing probes. Au NRs were prepared by a seed-mediated growth process and AuNR@Ag nanostructures were synthesized by growing Ag nanoshells on Au NRs. Successful coating of Ag nanoshells on the surface of Au NRs was demonstrated with TEM, EDS, and UV-vis spectrometer. By increasing the overall amount of the deposited Ag on Au NRs, the localized surface plasmon resonance (LSPR) band was significantly blue-shifted, which allowed tuning across the visible spectrum. The sensing mechanism relies on the redox reaction between Cr(VI) ions and Ag nanoshells on Au NRs. As the concentration of Cr(VI) ions increased, more significant red-shift of the longitudinal peak and intensity decrease of the transverse peak could be observed using UV-vis spectrometer. Several parameters such as concentration of CTAB, thickness of the Ag nanoshells and pH of the sample were carefully optimized to determine Cr(VI) ions. Under optimized condition, this method showed a low detection limit of 0.4 µM and high selectivity towards Cr(VI) over other metal ions, and the detection range of Cr(VI) was tuned by controlling thickness of the Ag nanoshells. From multiple evaluations in real sample, it is clear that this method is a promising Cr(VI) ion colorimetric sensor with rapid, sensitive, and selective sensing ability.

TSPO-targeted NIR-fluorescent ultra-small iron oxide nanoparticles for glioblastoma imaging.

The translocator protein 18 kDa (TSPO) is mainly located in outer membrane of mitochondria and results highly expressed in a variety of tumor including breast, colon, prostate, ovarian and brain (such as glioblastoma). Glioblastoma multiforme (GBM) is the most common and lethal type of primary brain tumor. Although GBM patients had currently available therapies, the median survival is <14 months. Complete surgical resection of GBM is critical to improve GBM treatment. In this study, we performed the one-step synthesis of water-dispersible ultra-small iron oxide nanoparticles (USPIONs) and combine them with an imidazopyridine based TSPO ligand and a fluorescent dye. The optical and structural characteristics of TSPO targeted-USPIONs were properly evaluated at each step of preparation demonstrating the high colloidal stability in physiological media and the ability to preserve the relevant optical properties in the NIR region. The cellular uptake in TSPO expressing cells was assessed by confocal microscopy. The TSPO selectivity was confirmed in vivo by competition studies with the TSPO ligand PK 11195. In vivo fluorescence imaging of U87-MG xenograft models were performed to highlight the great potential of the new NIR imaging nanosystem for diagnosis and successful delineation of GBM.

In vivo delineation of glioblastoma by targeting tumor-associated macrophages with near-infrared fluorescent silica coated iron oxide nanoparticles in orthotopic xenografts for surgical guidance.

Glioblastoma multiforme (GBM) is the most aggressive and lethal type of human brain cancer. Surgery is a current gold standard for GBM treatment but the complete surgical resection of GBM is almost impossible due to their diffusive characteristics into surrounded normal brain tissues. There is an urgent need to develop a sensitive imaging tool for accurate delineation of GBM in the operating room to guide surgeons. Here we illustrate the feasibility of using near-infrared fluorescent silica coated iron oxide nanoparticles (NF-SIONs) with high water dispersion capacity and strong fluorescence stability for intraoperative imaging of GBM by targeting tumor-associated macrophages. Abundant macrophage infiltration is a key feature of GBM margins and it is well associated with poor prognosis. We synthesized NF-SIONs of about 37 nm to maximize endocytosis activity for macrophage uptake. The NF-SIONs selectively visualized tumor-associated macrophage populations by in vitro live-cell imaging and in vivo fluorescence imaging. In the orthotopic GBM xenograft models, the NF-SIONs could successfully penetrate blood-brain barrier and delineated tumor burden specifically. Taken together, this study showcased the potential applications in GBM treatment for improved intraoperative staging and more radical surgery as well as dual modality benefit in order to circumvent previous clinical failure.

Facile scalable synthesis of highly monodisperse small silica nanoparticles using alkaline buffer solution and their application for efficient sentinel lymph node mapping.

Cancer nanomedicine involving nanotechnology-based drugs and in vivo imaging agents is an active field of nanoscience that provides new ways of enhancing therapeutic and diagnostic efficacy. Translating cancer nanomedicine mainly comes from rational and scalable design of nanoparticles to achieve versatile properties including specific size because nanomaterials whose properties confer unique advantages can only optimize clinical impact. Here, a facile scalable synthesis of highly monodisperse small silica nanoparticles was developed by screening various alkaline buffer solutions as catalysts. The size of silica nanoparticles ranging from 7 to 30 nm was finely controlled by varying the reaction temperature. Moderate sized silica nanoparticles in the range of 30 to 50 nm and large sized silica nanoparticles (>100 nm) were readily synthesized by in situ adding tetraethylorthosilicate (TEOS) and applying the Stöber method in the reaction solution using small silica nanoparticles as the seeds, respectively. Having shown the ability to precisely synthesize size controlled silica nanoparticles with a process compatible with good manufacturing practices, we performed in vivo fluorescence imaging and immunofluorescence analysis of sentinel lymph nodes (SLNs) with the synthesized nanoparticles having different sizes to investigate the size effect for effective identification of SLNs. The synthesized nanoparticles with a diameter of 12 nm showed effective SLN uptake within 10 min after intradermal injection both in noninvasive and in intraoperative imaging mode and were localized evenly inside the SLN, whereas the 120 nm sized nanoparticles failed to identify the SLN with noninvasive imaging at 10 min post-injection and distributed only in the medulla region not in the superficial cortex of the SLN. Taken together, a new facile scalable synthesis technique to achieve fine size controlling capability from very small silica nanoparticles (7 nm) was developed and it made possible to investigate the optimal size of nanoparticles for efficient SLN mapping which is still controversial.

Synthesis of Cu3Sn alloy nanocrystals through sequential reduction induced by gradual increase of the reaction temperature.

Cu3Sn alloy nanocrystals are synthesized by sequential reduction of Cu and Sn precursors through a gradual increase of the reaction temperature. By transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), UV/Vis spectroscopy, and X-ray diffraction (XRD) analyses, the alloy formation mechanism of Cu3Sn nanocrystals has been studied. The incremental increase of the reaction temperature sequentially induces the reduction of Sn, the diffusion of Sn into the preformed Cu nanocrystals, resulting in the intermediate phase of Cu-Sn alloy nanocrystals, and then the formation of Cu3Sn alloy nanocrystals. We anticipate that the synthesis of Cu3Sn alloy nanocrystals encourages studies toward the synthesis of various alloy nanomaterials.

One-step facile solvothermal synthesis of copper ferrite-graphene composite as a high-performance supercapacitor material.

In this work, we reported a facile approach to prepare a uniform copper ferrite nanoparticle-attached graphene nanosheet (CuFe2O4-GN). A one-step solvothermal method featuring the reduction of graphene oxide and formation of CuFe2O4 nanoparticles was efficient, scalable, green, and controllable. The composite nanosheet was fully characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS), which demonstrated that CuFe2O4 nanoparticles with a diameter of approximately 100 nm were densely and compactly deposited on GN. To investigate the formation mechanism of CuFe2O4-GN, we discussed in detail the effects of a series of experimental parameters, including the concentrations of the precursor, precipitation agent, stabilizer agent, and graphene oxide on the size and morphology of the resulting products. Furthermore, the electrochemical properties of the CuFe2O4-GN composite were studied by cyclic voltammetry and galvanostatic charge-discharge measurements. The composite showed high electrochemical capacitance (576.6 F·g(-1) at 1 A·g(-1)), good rate performance, and cycling stability. These results demonstrated that the composite, as a kind of electrode materials, had a high specific capacitance and good retention. The versatile CuFe2O4-GN holds great promise for application in a wide range of electrochemical fields because of the remarkable synergistic effects between CuFe2O4 nanoparticles and graphene.

Facile synthesis of oxidation-resistant copper nanowires toward solution-processable, flexible, foldable, and free-standing electrodes.

Oxidation-resistant copper nanowires (Cu NWs) are synthesized by a polyol reduction method. These Cu NWs show excellent oxidation resistance, good dispersibility, and have a low sintering temperature. A Cu NW-based flexible, foldable, and free-standing electrode is fabricated by filtration and a sintering process. The electrode also exhibits high electrical conductivity even bending, folding, and free-standing.