Catalytic Nanoparticles in Biomedical Applications: Exploiting Advanced Nanozymes for Therapeutics and Diagnostics.

Catalytic nanoparticles (CNPs) as heterogeneous catalyst reveals superior activity due to their physio-chemical features, such as high surface-to-volume ratio and unique optical, electric, and magnetic properties. The CNPs, based on their physio-chemical nature, can either increase the reactive oxygen species (ROS) level for tumor and antibacterial therapy or eliminate the ROS for cytoprotection, anti-inflammation, and anti-aging. In addition, the catalytic activity of nanozymes can specifically trigger a specific reaction accompanied by the optical feature change, presenting the feasibility of biosensor and bioimaging applications. Undoubtedly, CNPs play a pivotal role in pushing the evolution of technologies in medical and clinical fields, and advanced strategies and nanomaterials rely on the input of chemical experts to develop. Herein, a systematic and comprehensive review of the challenges and recent development of CNPs for biomedical applications is presented from the viewpoint of advanced nanomaterial with unique catalytic activity and additional functions. Furthermore, the biosafety issue of applying biodegradable and non-biodegradable nanozymes and future perspectives are critically discussed to guide a promising direction in developing span-new nanozymes and more intelligent strategies for overcoming the current clinical limitations.

Prussian blue analog with separated active sites to catalyze water driven enhanced catalytic treatments.

Chemodynamic therapy (CDT) uses the Fenton or Fenton-like reaction to yield toxic ‧OH following H2O2 → ‧OH for tumoral therapy. Unfortunately, H2O2 is often taken from the limited endogenous supply of H2O2 in cancer cells. A water oxidation CoFe Prussian blue (CFPB) nanoframes is presented to provide sustained, external energy-free self-supply of ‧OH from H2O to process CDT and/or photothermal therapy (PTT). Unexpectedly, the as-prepared CFPB nanocubes with no near-infrared (NIR) absorption is transformed into CFPB nanoframes with NIR absorption due to the increased Fe3+-N ≡ C-Fe2+ composition through the proposed proton-induced metal replacement reactions. Surprisingly, both the CFPB nanocubes and nanoframes provide for the self-supply of O2, H2O2, and ‧OH from H2O, with the nanoframe outperforming in the production of ‧OH. Simulation analysis indicates separated active sites in catalyzation of water oxidation, oxygen reduction, and Fenton-like reactions from CFPB. The liposome-covered CFPB nanoframes prepared for controllable water-driven CDT for male tumoral mice treatments.

Engineering H2 O2 and O2 Self-Supplying Nanoreactor to Conduct Synergistic Chemiexcited Photodynamic and Calcium-Overloaded Therapy in Orthotopic Hepatic Tumors.

Photodynamic therapy (PDT) is traditionally ineffective for deeply embedded tumors due to the poor penetration depth of the excitation light. Chemiluminescence resonance energy transfer (CRET) has emerged as a promising mode of PDT without external light. To date, related research has frequently used endogenous hydrogen peroxide (H2 O2 ) and oxygen (O2 ) inside the solid tumor microenvironment to trigger CRET-mediated PDT. Unfortunately, this significantly restricts treatment efficacy and the development of further biomedical applications because of the limited amounts of endogenous H2 O2 and O2 . Herein, a nanohybrid (mSiO2 /CaO2 /CPPO/Ce6: mSCCC) nanoparticle (NP) is designed to achieve synergistic CRET-mediated PDT and calcium (Ca2+ )-overload-mediated therapy. The calcium peroxide (CaO2 ) formed inside mesoporous SiO2 (mSC) with the inclusion of the chemiluminescent agent (CPPO) and photosensitizer (Ce6) self-supplies H2 O2 , O2 , and Ca2+ allowing for the subsequent treatments. The Ce6 in mSCCC NPs is excited by chemical energy in situ following the supply of H2 O2 and O2 to produce singlet oxygen (1 O2 ). The nanohybrid NPs are coated with stearic acid to avoid decomposition during blood circulation through contact with aqueous environment. This nanohybrid shows promising performance in the generation of 1 O2 for external light-free PDT and the release of Ca2+ ions for Ca2+ -overloaded therapy against orthotopic hepatocellular carcinoma.

Synchronization of Nanoparticle Sensitization and Radiosensitizing Chemotherapy through Cell Cycle Arrest Achieving Ultralow X-ray Dose Delivery to Pancreatic Tumors.

Pancreatic cancer is among the leading causes of cancer-related death and remains a formidable therapeutic challenge. To date, surgical resection and chemotherapy have been the standards of care. Methotrexate (MTX), which is recognized as a refractory drug for pancreatic cells, was conjugated to the surface of LiYF4:Ce3+ nanoparticles (NP-MTX) through a photocleavable linker molecule. When LiYF4:Ce3+ NPs are stimulated by X-rays, they emit light, which induces the photocleavage of the photolabile linker molecule to release MTX. MTX can target pancreatic tumors, which overexpress folic acid (FA) receptors and are internalized into the cell through receptor-mediated endocytosis. The synergistic effect of the NP-MTX treatment initiated by X-ray irradiation occurs due to the combination of nanoparticle sensitization and the radiosensitizing chemotherapy of the photocleaved MTX molecule. This dual sensitization effect mediated by NP-MTX enabled 40% dose enhancement, which corresponded with an increase in the generation of cytotoxic cellular reactive oxygen species (ROS) and enhanced S phase arrest within the cell cycle. The delivery of an ultralow radiation dose of 0.1 Gy resulted in the photocleavage of MTX from NP-MTX, and this strategy demonstrated in vivo efficacy against AsPC-1 and PANC-1 xenografted pancreatic tumors.

Low Dose of X-Ray-Excited Long-Lasting Luminescent Concave Nanocubes in Highly Passive Targeting Deep-Seated Hepatic Tumors.

Chromium-doped zinc gallate, ZnGa2 O4 :Cr3+ (ZGC), is viewed as a long-lasting luminescence (LLL) phosphor that can avoid tissue autofluorescence interference for in vivo imaging detection. ZGC is a cubic spinel structure, a typical agglomerative or clustered morphology lacking a defined cubic shape, but a sphere-like feature is commonly obtained for the nanometric ZGC. The substantial challenge remains achieving a well-defined cubic feature in nanoscale. The process by which dispersed and well-defined concave cubic ZGC is obtained is described, exhibiting much stronger LLL in UV and X-ray excitation for the dispersed cubic ZGC compared with the agglomerative form that cannot be excited using X-rays with a low dose of 0.5 Gy. The cubic ZGC reveals a specific accumulation in liver and 0.5 Gy used at the end of X-ray excitation is sufficient for imaging of deep-seated hepatic tumors. The ZGC nanocubes show highly passive targeting of orthotopic hepatic tumors.

High-Performance Electron Field Emitters and Microplasma Cathodes Based on Conductive Hybrid Granular Structured Diamond Materials.

High-performance diamond electron field emitters (EFEs) with extremely low turn-on field (E0 = 1.72 V/µm) and high current density (1.70 mA/cm2 at an applied field of 3.86 V/µm) were successfully synthesized by using a modified two-step microwave plasma chemical deposition process. Such emitters possess EFE properties comparable with most of carbon- or semiconductor-based EFE materials, but with markedly better lifetime stability. The superb EFE behavior of these materials was achieved owing to the reduction in the diamond-to-Si interfacial resistance and the increase in the conductivity of the bulk diamond films (HBD-400 V) via the applications of high bias voltage during the preparation of the ultrananocrystalline diamond (UNCD) primary layer and the subsequent plasma post-treatment (PPT) process, respectively. The superior EFE properties along with enhanced robustness of HBD-400 V films compared with the existing diamond-based EFE materials rendered these materials of greater potential for applications in high brightness display and multifunctional microplasma.

Defect structure and optical phonon confinement in ultrananocrystalline BixSn1-xO2 (x = 0, 0.03, 0.05, and 0.08) synthesized by a sonochemical method.

We report the structure of defect and the oxygen vacancy-induced optical phonon confinement in phase pure tetragonal rutile crystal structured ultrananocrystalline BixSn1-xO2 (x = 0, 0.03, 0.05, 0.08) with high surface area synthesized by sonochemical method. As the Bi ion incorporates into the SnO2 host lattice, it replaces the Sn ions marked by the lattice expansion, which leads to the formation of oxygen vacancies so as to maintain charge neutrality. The grain size reduces from 6 nm to 3 nm with increase in Bi content from 0% to 8%. The size effect and the increased oxygen vacancy concentration were found to induce phonon confinement within the grain. This has led to interesting changes in the vibrational spectra of the ultrananocrystalline BixSn1-xO2 as the size reduces below 9 nm. Absence of periodicity beyond this critical particle size relaxes the zone-centre optical phonon selection rule, causing the Raman spectrum to have contributions also from phonons away from the Brillouin-zone centre. The structure of defects, such as the in-plane, bridging and sub-bridging oxygen vacancies present, was confirmed using Raman spectroscopic analysis. The reason for enhancement in photoluminescence behaviour with increased Bi content is discussed. The energy band gap was found to be wider (∼4 eV) compared to the bulk and reveals an increasing trend as a function of Bi%. The increase in band gap with decrease in particle size marks the quantum confinement effect. The variation of band gap upon doping is due to the BM shift effect, which arises as a result of the increase in carrier concentration.

Heterogranular-Structured Diamond-Gold Nanohybrids: A New Long-Life Electronic Display Cathode.

In the age of hand-held portable electronics, the need for robust, stable and long-life cathode materials has become increasingly important. Herein, a novel heterogranular-structured diamond-gold nanohybrids (HDG) as a long-term stable cathode material for field-emission (FE) display and plasma display devices is experimentally demonstrated. These hybrid materials are electrically conductive that perform as an excellent field emitters, viz. low turn-on field of 2.62 V/µm with high FE current density of 4.57 mA/cm(2) (corresponding to a applied field of 6.43 V/µm) and prominently high lifetime stability lasting for 1092 min revealing their superiority on comparison with the other commonly used field emitters such as carbon nanotubes, graphene, and zinc oxide nanorods. The process of fabrication of these HDG materials is direct and easy thereby paving way for the advancement in next generation cathode materials for high-brightness FE and plasma-based display devices.

High Stability Electron Field Emitters Synthesized via the Combination of Carbon Nanotubes and N2-Plasma Grown Ultrananocrystalline Diamond Films.

An electron field emitter with superior electron field emission (EFE) properties and improved lifetime stability is being demonstrated via the combination of carbon nanotubes and the CH4/N2 plasma grown ultrananocrystalline diamond (N-UNCD) films. The resistance of the carbon nanotubes to plasma ion bombardment is improved by the formation of carbon nanocones on the side walls of the carbon nanotubes, thus forming strengthened carbon nanotubes (s-CNTs). The N-UNCD films can thus be grown on s-CNTs, forming N-UNCD/s-CNTs carbon nanocomposite materials. The N-UNCD/s-CNTs films possess good conductivity of σ = 237 S/cm and marvelous EFE properties, such as low turn-on field of (E0) = 3.58 V/µm with large EFE current density of (J(e)) = 1.86 mA/cm(2) at an applied field of 6.0 V/µm. Moreover, the EFE emitters can be operated under 0.19 mA/cm(2) for more than 350 min without showing any sign of degradation. Such a superior EFE property along with high robustness characteristic of these combination of materials are not attainable with neither N-UNCD films nor s-CNTs films alone. Transmission electron microscopic investigations indicated that the N-UNCD films contain needle-like diamond grains encased in a few layers of nanographitic phase, which enhanced markedly the transport of electrons in the N-UNCD films. Moreover, the needle-like diamond grains were nucleated from the s-CNTs without the necessity of forming the interlayer that facilitate the transport of electrons crossing the diamond-to-Si interface. Both these factors contributed to the enhanced EFE behavior of the N-UNCD/s-CNTs films.

Microstructural Evolution of Nanocrystalline Diamond Films Due to CH4/Ar/H2 Plasma Post-Treatment Process.

Plasma post-treatment process was observed to markedly enhance the electron field emission (EFE) properties of ultrananocrystalline diamond (UNCD) films. TEM examinations reveal that the prime factor which improves the EFE properties of these films is the coalescence of ultrasmall diamond grains (∼5 nm) forming large diamond grains about hundreds of nanometers accompanied by the formation of nanographitic clusters along the grain boundaries due to the plasma post-treatment process. OES studies reveal the presence of large proportion of atomic hydrogen and C2 (or CH) species, which are the main ingredients that altered the granular structure of the UNCD films. In the post-treatment process, the plasma interacts with the diamond films by a diffusion process. The recrystallization of diamond grains started at the surface region of the material, and the interaction zone increased with the post-treatment period. The entire diamond film can be converted into a nanocrystalline granular structure when post-treated for a sufficient length of time.

Unique sharp photoluminescence of size-controlled sonochemically synthesized zirconia nanoparticles.

The present study explores the features of tetragonally stabilized polycrystalline zirconia nanophosphors prepared by a sonochemistry based synthesis from zirconium oxalate precursor complex. The sonochemically prepared pristine zirconia, 3 mol%, 5 mol% and 8 mol% yttrium doped zirconia nanophosphors were characterized using thermo-gravimetric analysis (TGA), X-ray diffraction (XRD), Raman spectroscopy, field emission scanning electron microscopy (FE-SEM) with energy dispersive X-ray spectroscopy (EDS), transmission electron microscopy (TEM), diffuse reflectance spectroscopy (DRS) and photoluminescence spectroscopy (PL). The reaction mechanism of formation of zirconia nanophosphors is discussed in detail. The probable sonochemical formation mechanism is being proposed. Stabilization of tetragonal phase of pristine zirconia even at room temperature was effectively established by controlling the particle size using ultrasonic waves. Improved phase purity and good surface morphology of the nanophosphors is being achieved via sonochemical route. FE-SEM micrographs reveal that the nanoparticles have uniform spherical shape and size. The narrow particle size distribution (∼15-25 nm) of the zirconia nanoparticles was found from FE-SEM statistical analysis and further confirmed by TEM. Zirconia nanophosphors exhibit a wide energy band gap and which was found to vary with yttrium dopant concentration. The highlight of the present study is the synthesis of novel nanocrystalline ZrO2 and Y-ZrO2 phosphor which simultaneously emits extremely sharp as well as intense UV, violet and cyan light on exciting the host atom. The yttrium ion dopant further enhances the photoluminescence property of zirconia. These nanocrystalline phosphors are likely to have remarkable optical applications as light emitting UV-LEDs, UV lasers and multi color displays.