In vivo guiding nitrogen-doped carbon nanozyme for tumor catalytic therapy

The extended Stӧber method for synthesizing nitrogen-doped porous carbon nanospheres supported Pt nanoparticles towards methanol oxidation in alkaline media

Porous carbon materials produced by biomass have been widely studied for high performance supercapacitor due to their abundance, low price, and renewable. In this paper, the series of nitrogen-doped hierarchical porous carbon nanospheres (HPCN)/polyaniline (HPCN/PANI) nanocomposites is reported, which is prepared via in-situ polymerization. A novel approach with one-step pyrolysis of wheat flour mixed with urea and ZnCl2 is proposed to prepare the HPCN with surface area of 930 m2/g. Ultrathin HPCN pyrolysised at 900°C (~3 nm in thickness) electrode displays a gravimetric capacitance of 168 F/g and remarkable cyclability with losing 5% of the maximum capacitance after 5,000 cycles. The interconnected porous texture permits depositing of well-ordered polyaniline nanorods and allows a fast absorption/desorption of electrolyte. HPCN/PANI with short diffusion pathway possesses high gravimetric capacitance of 783 F/g. It can qualify HPCN/PANI to be used as cathode in assembling asymmetric supercapacitor with HPCN as anode, and which displays an exceptional specific capacitance of 81.2 F/g. Moreover, HPCN/PANI//HPCN device presents excellent cyclability with 88.4% retention of initial capacity over 10,000 cycles. This work will provide a simple and economical protocol to prepare the sustainable biomass materials based electrodes for energy storage applications.

A completely new type of nitrogen-doped polymer nanosphere and the derived nitrogen-doped porous carbon nanospheres were produced by taking 2,4-diamino-6-hydroxypyrimidine as the precursor. When functioning as electrode materials, they demonstrated extraordinary electrochemical performance, offering a powerful candidate for supercapacitors.

Nitrogen-doped porous carbon nanospheres (PCNs) with a high surface area were prepared by chemical activation of nonporous carbon nanospheres (CNs). CNs were obtained via carbonization of polypyrrole nanospheres (PNs) that were synthesized by ultrasonic polymerization of pyrrole. The catalysts Pt/PCN, Pt/CN, and Pt/PN were prepared by depositing Pt nanoparticles on supports PCNs, CNs, and PNs, respectively, using ethylene glycol chemical reduction. Nitrogen adsorption, X-ray diffraction, thermogravimetric analysis, transmission electron microscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy were employed to characterize samples. It was found that after chemical activation using KOH, PCNs containing N functional groups (mainly N-6 and N-Q) possessed a microporous structure with a high surface area of 1010 m2/g and a particle size of less than 100 nm. The electrochemical properties of samples Pt/PCN, Pt/CN, and Pt/PN, together with commercial catalysts E-TEK (40 wt % Pt loading), were comparatively investigated in methanol oxidation reaction (MOR) and oxygen reduction reaction (ORR) for fuel cells. The results showed that the catalytic activity of Pt/PN toward both reactions at room temperature is almost negligible possibly due to the poor conductivity of support PNs proven by impedance spectroscopy, in contrast with some literature reports. Compared to Pt/CN and E-TEK catalyst, Pt/PCN revealed an enhanced mass activity in ORR and MOR because of the high dispersion of small Pt nanoparticles, the presence of nitrogen species, and developed microporous structure of support PCNs.

Glioblastoma (GBM) is the most common primary brain cancer in adults. Despite the remarkable advancements in recent years in the realm of cancer diagnosis and therapy, regrettably, GBM remains the most lethal form of brain cancer. In this view, the fascinating area of nanotechnology has emerged as an innovative strategy for developing novel nanomaterials for cancer nanomedicine, such as artificial enzymes, termed nanozymes, with intrinsic enzyme-like activities. Therefore, this study reports for the first time the design, synthesis, and extensive characterization of innovative colloidal nanostructures made of cobalt-doped iron oxide nanoparticles chemically stabilized by a carboxymethylcellulose capping ligand (i.e., Co-MION), creating a peroxidase-like (POD) nanozyme for biocatalytically killing GBM cancer cells. These nanoconjugates were produced using a strictly green aqueous process under mild conditions to create non-toxic bioengineered nanotherapeutics against GBM cells. The nanozyme (Co-MION) showed a magnetite inorganic crystalline core with a uniform spherical morphology (diameter, 2R = 6-7 nm) stabilized by the CMC biopolymer, producing a hydrodynamic diameter (HD) of 41-52 nm and a negatively charged surface (ZP~-50 mV). Thus, we created supramolecular water-dispersible colloidal nanostructures composed of an inorganic core (Cox-MION) and a surrounding biopolymer shell (CMC). The nanozymes confirmed the cytotoxicity evaluated by an MTT bioassay using a 2D culture in vitro of U87 brain cancer cells, which was concentration-dependent and boosted by increasing the cobalt-doping content in the nanosystems. Additionally, the results confirmed that the lethality of U87 brain cancer cells was predominantly caused by the production of toxic cell-damaging reactive oxygen species (ROS) through the in situ generation of hydroxyl radicals (·OH) by the peroxidase-like activity displayed by nanozymes. Thus, the nanozymes induced apoptosis (i.e., programmed cell death) and ferroptosis (i.e., lipid peroxidation) pathways by intracellular biocatalytic enzyme-like activity. More importantly, based on the 3D spheroids model, these nanozymes inhibited tumor growth and remarkably reduced the malignant tumor volume after the nanotherapeutic treatment (ΔV~40%). The kinetics of the anticancer activity of these novel nanotherapeutic agents decreased with the time of incubation of the GBM 3D models, indicating a similar trend commonly observed in tumor microenvironments (TMEs). Furthermore, the results demonstrated that the 2D in vitro model overestimated the relative efficiency of the anticancer agents (i.e., nanozymes and the DOX drug) compared to the 3D spheroid models. These findings are notable as they evidenced that the 3D spheroid model resembles more precisely the TME of "real" brain cancer tumors in patients than 2D cell cultures. Thus, based on our groundwork, 3D tumor spheroid models might be able to offer transitional systems between conventional 2D cell cultures and complex biological in vivo models for evaluating anticancer agents more precisely. These nanotherapeutics offer a wide avenue of opportunities to develop innovative nanomedicines for fighting against cancerous tumors and reducing the frequency of severe side effects in conventionally applied chemotherapy-based treatments.

In ischemic stroke, microglia adopt a pro-inflammatory M1-like phenotype, which plays a pivotal role in the excessive production of nitric oxide radical (NO). The elevated levels of NO contribute to caspase-mediated apoptosis, resulting in significant disruption of cerebral tissue architecture and consequent loss of brain function. In this study, we demonstrate that iron oxide nanoparticles (IONPs) with intrinsic enzyme-like activities can effectively scavenge NO by forming a nitrosyl-metal complex. Specifically, 6nm iron oxide nanoparticle (IONP6) exhibits enzyme-like activities, superoxide dismutase (SOD) and catalase (CAT), thus potentially possessing the ability to scavenge the Reactive Oxygen and Nitrogen Species (RONS), especially the ability to scavenge NO. Furthermore, we show that IONP6 promotes the polarization of microglia toward the M2 phenotype, thereby alleviating neuroinflammation in both in vitro oxygen and glucose deprivation (OGD) and in vivo permanent middle cerebral artery occlusion (pMCAO) stroke models. This is achieved through the modulation of the HIF-1α/TIM-3 signaling axis in stroke rats. Additionally, IONP6 administration significantly reduces infarct size and improves neurological outcomes in stroke rats. Our findings position IONP6 as a promising drug-free therapeutic agent for stroke, capable of regulating microglial polarization and mitigating secondary injury caused by the inflammatory cascade induced by NO.

A “green nano” strategy was extended to prepare monodisperse polypyrrole (PPy) nanospheres with tunable sizes via simply adjusting pyrrole monomer's concentration. And a linear model was obtained and used to predict the diameter of PPy nanosphere. Nitrogen-doped carbon nanospheres (NCSs) with well-controlled diameters were further synthesized through direct carbonzilation of harvested PPy nanospheres, which demonstrated a facile route for the preparation of highly dispersible NCSs with controlled sizes. Then the potential electrochemical response of as-fabricated NCSs toward food additive-Sunset yellow (SY) was explored. NCSs with medium size (M-NCSs) showed the best electrochemical performance and an ultra-high sensitivity of 679.16 A M−1 cm−2 and lower detection limit of 0.95 nM were gained. This study therefore provides a facile route to high quality, uniform, and size-controlled PPy nanospheres and NCSs, which are promising to be applied to electrochemical and other fields.

Electrocatalytic reduction of carbon dioxide in confined microspace utilizing single nickel atom decorated nitrogen-doped carbon nanospheres

Oxygen reduction reaction (ORR) at catalyst surface is the key kinetic limiting step in fuel cells that influence the overall cell performance in the energy conversion process. Rational design of the carbon supports with unique morphology and controllable porosity is challenging and significant for efficient and durable oxygen reduction electrocatalysis. Nitrogen-doped carbon nanospheres with uniform size and precise control over mesopores and micropores have been derived from mussel-inspired biomimetic polydopamine through a facile colloidal synthesis method and subsequent high-temperature pyrolysis. The unique surface structure of this nitrogen-doped carbon also dictated the morphologies of the deposited platinum nanoparticles, alleviating the particle dissolution, detachment, and agglomeration issue, which are main factors for catalyst degradation in working conditions. The ORR activity and durability of this electrocatalysts were studied in both rotational disk electrode (RDE) system and membrane electrode assembly (MEA), and a detailed structure-property relationship between porosity of carbon supports, Pt morphologies and fuel cell ORR performance was uncovered. This work is informative to researchers working in electrochemical materials field for developing efficient and robust electrocatalyst supports.Acknowledgement: This research was supported by the Hydrogen and Fuel Cell Technologies Office (HFTO), Office of Energy Efficiency and Renewable Energy, US Department of Energy (DOE) through the Million Mile Fuel Cell Truck (M2FCT) consortium, technology managers G. Kleen and D. Papageorgopoulos.

Nanomaterials with intrinsic enzyme-like activity have gained substantial scientific attention as viable substitutes to natural biological enzymes owing to their cheap price and great stability. Numerous artificial enzyme mimics have been employed effectively in sectors such as sensing, environmental processing, and cancer treatment. In this study, novel nitrogen-doped porous carbon nanomaterials (CPs) were produced by modifying polypyrrole with magadiite using chemical oxidative polymerization and calcination methods. The obtained nitrogen-doped porous carbon nanomaterials exhibited improved peroxidase-like activity, which catalyzed the oxidation of 3,3,5,5-tetramethylbenzidine (TMB) in the presence of hydrogen peroxide (H2O2) to produce colorful compounds. Kinetic investigation revealed that the affinity for TMB of nitrogen-doped porous carbon peroxidase mimics was higher than that of genuine horseradish peroxidase (HRP). In addition, a sensitive assay with encouraging performance for the colorimetric detection of ascorbic acid (AA) was successfully fabricated employing nitrogen-doped porous carbon nanomaterials as peroxidase mimics. The results were satisfactory and demonstrated its potential application in antioxidant detection.

Easy preparation of nitrogen-doped porous carbon nanospheres and their application in supercapacitors

Calorie Restriction Reduces Oxidative Stress by SIRT3-Mediated SOD2 Activation

Given the promising prospect of aggregation-induced emission luminogens (AIEgens) in fluorescence assays, it is interesting and significant to endow AIEgens with molecular recognition capability (such as enzyme-like activity). Here, an AIE nanomaterial with intrinsic enzyme-like activity (named as "AIEzyme") is designed and synthesized via a facile coordination polymerization of Zr4+ and AIE ligands. AIEzyme possesses enhanced and stable fluorescence in different solvents because of the AIE effect of ligands in the rigid structure of a coordination polymer. On the other hand, the organophosphorus hydrolase (OPH)-mimicking activity of AIEzyme exhibits excellent affinity and specific activity. Interestingly, the OPH-like activity can quench the inherent fluorescence of AIEzyme by the hydrolysate of a typical organophosphorus nerve agent (OPNA), diethyl-4-nitrophenylphosphate. Due to the sensitive activity-induced quenching effect for AIE, the self-reporting fluorescence assay method based on AIEzyme was established, which shows ultrahigh sensitivity, high selectivity, good storage stability, and acceptable reliability for a real sample assay. Moreover, the simultaneous colorimetric method broadens the detection range and the application scenarios. The proposed assay method avoided the interference of O2 during detection because the OPH-like activity does not derive from the generation of ROS. As a bonus, AIEzyme can also be used for the degradation of OPNAs by OPH-like activity, and the process can be self-monitored by AIE quenching. This work would provide a new opportunity for expanding the application of AIEgens and artificial enzymes by endowing AIEgens with enzyme-like activity.

Nanomaterials with enzyme-like activity, generally referred to as ‘nanozymes’, find myriad potential in various biomedical fields. More importantly, the nanoparticles that can functionally mimic the activity of cellular antioxidant enzymes attract tremendous interest owing to their possible therapeutic candidature in oxidative stress-mediated disorders. Oxidative stress culminating due to excess reactive oxygen species (ROS) level and dysregulated cellular antioxidant machinery is implicated in the development and progression of various pathophysiological disorders such as cancer, diabetes, cardiovascular and neurodegenerative diseases. Moreover, the optimum essentiality of ROS due to its pivotal role in cell signaling evokes the requirement of novel artificial antioxidant enzymes that can circumvent the detrimental effects of enhanced ROS levels without perturbing the basal redox status of cells. In recent years, the fast emanating artificial enzymes, i.e. nanozymes with antioxidant enzyme-like activity, has made tremendous progress with their broad applications in therapeutics, diagnostic medicine, bio-sensing, and immunoassay. Among various antioxidant nanoparticles reported till-date, the metal oxide nanozymes have emerged as the most efficient and successful candidates in mimicking the activity of first-line defense antioxidant enzymes, i.e. superoxide dismutase, catalase, and glutathione peroxidase. This review intends to exclusively highlight the development of representative metal oxide-based antioxidant nanozymes capable of maintaining the cellular redox homeostasis and their potential therapeutic significance.

Facile and scalable construction of nitrogen-doped lignin-based carbon nanospheres for high-performance supercapacitors