Small Nanoparticles Research Articles

Multifunctional hybrid oncolytic virus-mimicking nanoparticles for targeted induce of tumor-specific pyroptosis and enhanced anti-tumor immune response in melanoma

Pyroptosis, a newly discovered form of programmed cell death, has emerged as a promising antitumor approach by releasing pro-inflammatory cytokines and immunogenic substances upon cell rupture. However, non-specific pyroptosis potentially causes systemic damage to healthy tissues, and the heterogeneity of tumors limits the anti-tumor effect of pyroptosis. To address these challenges, we propose a simple yet powerful method for creating multifunctional hybrid oncolytic virus-mimicking nanovesicles (HVMNVs) that possess tumor-targeting capabilities, adjuvant activity, and the ability to evade immune clearance induced by virus modification. Based on this multifunctional nanovesicle, we developed a functional nanoparticle (HVMNVs@Fe-C) that significantly enhances the tumor targetability and cell uptake efficiency of the extremely small iron oxide nanoparticles (ESIONPs) and carbonyl cyanide m-chlorophenyl hydrazone (CCCP), leading to rapid tumor pyroptosis. More importantly, HVMNVs@Fe-C ingeniously achieves a synergistic effect by incorporating the adjuvantic and tumor-targeting properties of oncolytic viruses with the cell lytic and pro-inflammatory functions of pyroptosis in a single nanoparticle. This leads to a cascade of specific anti-tumor immune responses and reprogramming of the immunosuppressive tumor microenvironment, resulting in excellent tumor inhibition efficacy against primary melanoma growth and pulmonary metastasis. Overall, our novel strategy offers considerable promise for precisive targeted delivery and cancer immunotherapy.

Kilogram-Scale Synthesis of Extremely Small Gadolinium Oxide Nanoparticles as a T1-Weighted Contrast Agent for Magnetic Resonance Imaging.

Magnetic resonance imaging contrast agents are frequently used in clinics to enhance the contrast between diseased and normal tissues. The previously reported poly(acrylic acid) stabilized exceedingly small gadolinium oxide nanoparticles (ES-GdON-PAA) overcame the problems of commercial Gd chelates, but limitations still exist, i.e., high r2/r1 ratio, long blood circulation half-life, and no data for large scale synthesis and formulation optimization. In this study, polymaleic acid (PMA) is found to be an ideal stabilizer to synthesize ES-GdONs. Compared with ES-GdON-PAA, the PMA-stabilized ES-GdON (ES-GdON-PMA) has a lower r2/r1 ratio (2.05, 7.0 T) and a lower blood circulation half-life (37.51min). The optimized ES-GdON-PMA-9 has an exceedingly small particle size (2.1nm), excellent water dispersibility, and stability. A facile, efficient, and environmental friendly synthetic method is developed for large-scale synthesis of the ES-GdONs-PMA. The weight of the optimized freeze-dried ES-GdON-PMA-26 synthesized in a 20L of reactor reaches the kilogram level. The formulation optimization is also finished, and the concentrated ES-GdON-PMA-26 formulation (CGd=100mm) after high-pressure steam sterilization possesses eligible physicochemical properties (i.e., pH value, osmolality, viscosity, and density) for investigational new drug application.

In silico investigation on interaction of small Ag6 nano-particle cluster with tyramine neurotransmitter

The interaction of tyramine neurotransmitter with silver nano-particle (Ag6) cluster is explored in terms of the molecular structure, electronic properties and NBO analysis of tyramine-AgNPs bio-molecular conjugate. The adsorption mechanism of tyramine onto the Ag6 cluster has been investigated through computing of the electronic and geometrical properties in addition to the adsorption energies in various possible configurations. The magnitude of adsorption energy corresponding to the most favorable tyramine-Ag6 bio-molecular conjugate has been computed to be − 14.36 kcal/mol in the gas phase, which infers a good adsorption of tyramine with AgNPs cluster suggesting the practical applications of tyramine-AgNPs bio-molecular conjugates in bio-sensing, drug delivery, bio-imaging and other applications. Different electronic properties such as the energy gap of HOMO–LUMO, Fermi level and work function have been investigated in detail. Moreover, the effect of aqueous media on adsorption energy and electronic properties of the most favorable tyramine-AgNPs bio-molecular conjugate is investigated in order to understand the impact of the real biological situation.

First-principles molecular dynamics compression of small metallic nanoparticles

Whether the strength of materials keeps increasing, saturates or decreases when characteristic dimensions are reduced down to the nanometer scale remains an open question. To bring new insights, first principles molecular dynamics calculations are performed to model the compression of 1–2 nm aluminum nanoparticles with different shapes. We find that the plastic deformation occurs at high strains and stresses by a mechanism combining diffusive and displacive atomic displacements. This deformation mode is characterized by a slow dynamic and the partial or even complete recovery of crystalline order. The strength depends on the nanoparticles shape, and is in all cases significantly higher than the theoretical bulk strength. It is however substantially lower than values extrapolated using reported classical molecular dynamics investigations. Our results suggest that the strength saturates at low scales.

Enhanced Activity of Small Pt Nanoparticles Decorated with High-Loading Single Fe─N4 for Methanol Oxidation and Oxygen Reduction via the Assistive Active Sites Strategy.

Decorating platinum (Pt) with a single atom offers a promising approach to tailoring their catalytic activity. In this study, for the first time, an innovative assistive active sites (AAS) strategy is proposed to construct high-loading (3.46wt.%) single Fe─N4 as AAS, which are further hybridized with small Pt nanoparticles to enhance both oxygen reduction reaction (ORR) and methanol oxidation reaction (MOR) activities. For ORR, the target catalyst (Pt/HFeSA-HCS) exhibits a higher mass activity (MA) of 0.98AmgPt -1 and specific activity (SA) of 1.39mAcmPt -2 at 0.90V versus RHE. As for MOR, Pt/HFeSA-HCS shows exceptional MA (3.21AmgPt -1) and SA (4.27mAcmPt -2) at peak values, surpassing commercial Pt/C by 15.3 and 11.5 times, respectively. The underlying mechanism behind this AAS strategy is to find that in MOR, Fe─N4 promotes water dissociation, generating more *OH to accelerate the conversion of *CO to CO2. Meanwhile, in ORR, Fe─N4 acts as a competitor to adsorb *OH, weakening Pt─OH bonding and facilitating desorption of *OH on the Pt surface. Constructing AAS that can enhance dual functionality simultaneously can be seen as a successful "kill two birds with one stone" strategy.

Liposomal Delivery of an Immunostimulatory CpG Induces Robust Antitumor Immunity and Long-Term Immune Memory by Reprogramming Tumor-Associated Macrophages.

Tumor-associated macrophages (TAMs)-representative immune-suppressive cells in the tumor microenvironment (TME)-are known to promote tumor progression and metastasis, and thus are considered an attractive target for cancer therapy. However, current TAM-targeting strategies are insufficient to result in robust antitumor efficacy. Here, a small lipid nanoparticle encapsulating immunostimulatory CpG oligodeoxynucleotides (SLNP@CpG) is reported as a new immunotherapeutic modality that can reprogram TAMs and further bridge innate-to-adaptive immunity. It is found that SLNP@CpG treatment enhances macrophage-mediated phagocytosis of cancer cells and tumor antigen cross-presentation, and skews the polarization state of macrophages invitro. Intratumoral injection of SLNP@CpG into an established murine E.G7-OVA tumor model significantly suppresses tumor growth and considerably prolongs survival, completely eradicating tumors in 83.3% of mice. Furthermore, tumor-free mice resist rechallenge with E.G7-OVA cancer cells through induction of immunological memory and long-term antitumor immunity. SLNP@CpG even exerts antitumor efficacy in an aggressive B16-F10 melanoma model by remodeling TME toward immune stimulation and tumor elimination. These findings suggest that, by modulating the function of TAMs and reshaping an immunosuppressive TME, the SLNP@CpG nanomedicine developed here may become a promising immunotherapeutic option applicable to a variety of tumors.

Interfacial Effect-Induced Electrocatalytic Activity of Spinel Cobalt Oxide in Methanol Oxidation Reaction.

In this study, spinel cobalt oxide (Co3O4) nanoparticles without combining with any other metal atoms have been decorated through the influence of two hard templating agents, viz., zeolite-Y and carboxy-functionalized multiwalled carbon nanotubes (COOH-MWCNT). The adornment of the Co3O4 nanoparticles, through the combined impact of the aluminosilicate and carbon framework has resulted in quantum interference, causing the reversal of signatory Raman peaks of Co3O4. Apart from the construction of small Co3O4 nanoparticles at the interface of the two matrices, the particles were aligned along the direction of COOH-MWCNT. The catalyst Co3O4-Y-MWCNT exhibited excellent catalytic activity toward the methanol oxidation reaction (MOR) in comparison to Co3O4-Y, Co3O4-MWCNT, and bared Co3O4 with the current density of 0.92 A mg-1 at an onset potential of 1.33 V versus RHE. The material demonstrated persistent electrocatalytic activity up to 300 potential cycles and 20,000 s without substantial current density loss. High surface area of zeolite-Y in combination with the excellent conductivity of the COOH-MWCNT enhanced the electrocatalytic performance of the catalyst. The simplicity of synthesis, scale-up, and remarkable electrocatalytic activity of the catalyst Co3O4-Y-MWCNT provided an effective way toward the development of anode materials for direct methanol fuel cells.

Reductive amination of 1,6-hexanediol with a modified Ru/Al2O3 catalyst

The synthesis of 1,6–hexamethylenediamine via the reductive amination of 1,6–hexanediol is a fascinating green process and a challenging topic. We developed a kind of Ru/PRL(x)–Al2O3 catalyst for the reductive amination of 1,6–hexanediol, the active Ru species was highly dispersed and anchored by the CNx species formed from 1,10-phenanthroline (PRL). The Ru particle dispersion, electronic interaction, and acid–basic property as well as the catalytic mechanism and the rate determining step were discussed in detail. The new and more acid–base pairs formed, and the electron deficient Ru species and smaller nanoparticles are responsible for the improved catalytic performances of Ru/PRL–Al2O3 catalyst. The yield of 1,6–hexamethylenediamine could reach to 54%, which is the best results reported up to now. The present catalytic process is of great potential for industrial application as it is a green process compared to the traditional method for 1,6–hexamethylenediamine production.

A Novel Strategy for the Preparation of Supported Pd as an Efficient Catalyst for the Hydrogenation of Nitrobenzene in Mild Conditions

An advanced strategy was developed for the synthesis of molecular sieve-supported Pd catalysts. In this method, reductant containing C=C was in-situ prepared and pre-dispersed in the pore of the zeolites. The C=C group in the reductant can reduce the Pd2+ to Pd0 efficiently, leading to the formation of small and uniform Pd nanoparticles (~2 nm). The physical and chemical properties of the catalyst were characterized by XRD, TEM, XPS (ICP-OES), N2 isothermal adsorption-desorption, and H2-TPR. These catalysts showed high catalytic performance for the hydrogenation of nitrobenzene to aniline. All the TOFs for 1.5 Pd/Y, 1.5 Pd/ZSM-5, and 1.5 Pd/MOR with 1.5 wt% Pd loading are higher than 1000 h−1 at 30 °C and 0.1 MPa H2. Meanwhile, kinetic analysis for 2.0 Pd/Y was carried out, and an apparent activation energy of 28.88 kJ mol−1 was obtained, which is lower than most of the reported values in the literature. Furthermore, these catalysts were stable and recyclable.

The Origin of the Size Effect in the Oxidation of CO on Supported Palladium Nanoparticles

Two Pd/TiO2 catalysts with mean particle sizes of 1 and 3 nm were prepared and tested in the low-temperature oxidation of CO. It was found that the first catalyst with higher dispersion is more active. Turnover frequencies varied for these catalysts by almost six times. In contrast, the apparent activation energy of the oxidation of CO on the catalyst with smaller Pd nanoparticles was estimated at 76 kJ/mol, and for the catalyst with larger Pd nanoparticles at 58 kJ/mol. According to in situ XANES studies, the particle size effect originates from the oxidation of small palladium nanoparticles under reaction conditions, whereas larger nanoparticles are stable and consist of palladium atoms mainly in the metallic state. Palladium oxide is more active in the low-temperature oxidation of CO than metallic palladium. This means that the origin of size-dependent activity of Pd nanoparticles in the low-temperature oxidation of CO is associated with the change in the chemical composition of nanoparticles that leads to a change in the reaction mechanism and, as a result, in their activity.

Phase-field analysis of the effects of particle size, diffusivities, and mechanical properties on the cracking of silicon nanoparticle

In this study, a multiphysics model that reproduces the cracking of Si nanoparticle for a battery application was demonstrated. Two types of cracks appear on Si nanoparticle during lithiation. An essential condition for surface crack (SC) nucleation and propagation is a fast charging rate to form a high concentration gradient of lithium ions near the surface. A slower charging rate induces internal cracks (ICs) radiating from the center of the particle. The critical charging rates, at which SC or IC occurs, decrease rapidly with increasing particle radius. This indicates the difficulty of cracking of small nanoparticles, which is in a good agreement with the previous experimental results. Multiple cracks can appear in the particle, especially when the diffusivity is high. These cracks can be combined during the charging process, leading to the fracture or isolation of the particles. Additionally, two different peak stresses and Young's moduli from the literature were used considering their effects on the cracking of Si nanoparticle films. We believe our results provide a guideline for the fabrication and operation of Si nanoparticle-based anodes for lithium ion batteries.

Simulation of Microscopic Fracture Behavior in Nanocomposite Ceramic Tool Materials

In this paper, the microstructures of nanocomposite ceramic tool materials are represented through Voronoi tessellation. A cohesive element model is established to perform the crack propagation simulation by introducing cohesive elements with fracture criteria into microstructure models. Both intergranular and transgranular cracking are considered in this work. The influences of nanoparticle size, microstructure type, nanoparticle volume content and interface fracture energy are analyzed, respectively. The simulation results show that the nanoparticles have changed the fracture pattern from intergranular mode in single-phase materials to intergranular–transgranular–mixed mode. It is mainly the nanoparticles along grain boundaries that have an impact on the fracture pattern change in nanocomposite ceramic tool materials. Microstructures with smaller nanoparticles, in which there are more nanoparticles dispersed along matrix grain boundaries, have higher fracture toughness. Microstructures with a nanoparticle volume content of 15% have the most obvious transgranular fracture phenomenon and the highest critical fracture energy release rate. A strong interface is useful for enhancing the fracture toughness of nanocomposite ceramic tool materials.

Photoexcited state properties of N-ethylcarbazole-functionalized carbon dots in solution and in PVK polymer matrix

The adducts of N-ethylcarbazole (NEC) to small carbon nanoparticles prepared by microwave-assisted thermal processing are carbon dots (CDots) with NEC for the dot surface functionalization, thus NEC-CDots, which were shown previously for their high stability in the dot structure and properties. In this study, the optical absorptions and photoexcited state properties of NEC-CDots in solution and in poly(N-vinylcarbazole) (PVK) film matrix were evaluated by using optical spectroscopy methods, including those for fluorescence decays and lifetimes. The results suggest that the properties are largely unchanged from solution phase to the polymer matrix environment, very positive to their expected optoelectronic applications.

Comparative Analysis of the Physicochemical and Biological Characteristics of Freeze-Dried PEGylated Cationic Solid Lipid Nanoparticles.

Cationic solid-lipid nanoparticles (cSLNs) have become a promising tool for gene and RNA therapies. PEGylation (PEG) is crucial in enhancing particle stability and protection. We evaluated the impact of PEG on the physicochemical and biological characteristics of cholesteryl-oleate cSLNs (CO-cSLNs). Several parameters were analyzed, including the particle size, polydispersity index, zeta potential, shape, stability, cytotoxicity, and loading efficiency. Five different formulations with specific PEGs were developed and compared in both suspended and freeze-dried states. Small, homogeneous, and cationic suspended nanoparticles were obtained, with the Gelucire 50/13 (PEG-32 hydrogenated palm glycerides; Gelucire) and DSPE-mPEG2000 (1,2-distearoyl-phosphatidylethanolamine-methyl-polyethyleneglycol conjungate-2000; DSPE) formulations exhibiting the smallest particle size (~170 nm). Monodisperse populations of freeze-dried nanoparticles were also achieved, with particle sizes ranging from 200 to 300 nm and Z potential values of 30-35 mV. Notably, Gelucire again produced the smallest particle size (211.1 ± 22.4), while the DSPE and Myrj S100 (polyoxyethylene (100) stearate; PEG-100 Stearate) formulations had similar particle sizes to CO-cSLNs (~235 nm). The obtained PEGylated nanoparticles showed suitable properties: they were nontoxic, had acceptable morphology, were capable of forming SLNplexes, and were stable in both suspended and lyophilized states. These PEG-cSLNs are a potential resource for in vivo assays and have the advantage of employing cost-effective PEGs. Optimizing the lyophilization process and standardizing parameters are also recommended to maintain nanoparticle integrity.

Size Effect of Cu Nanoparticles in Cu/g-C3N4 Composites on Properties for Highly Efficient Photocatalytic Reduction of CO2 to Methanol.

The main goal of this work is to develop cheap photocatalysts for the efficient photocatalytic reduction of CO2 to methanol with water. A series of composites of Cu/g-C3N4 were prepared via a solvothermal method. Copper nanoparticle (Cu NP) size in Cu/g-C3N4 can be easily controlled by adjusting the synthesis temperature. The Cu/g-C3N4 material with the proper size of Cu NP (CuCN-100) had the best photocatalytic property (675 μmol·g-1·h-1) in reducing the amount of CO2 to methanol at room temperature under normal pressure. The particle size of Cu NPs is the key factor to improve the catalytic activity and stability because of the improved transfer and separation of photogenerated charges with the small Cu NPs. Although the sample with large Cu NPs (CuCN-200) initially gave a better activity than that of CuCN-100 due to the formation of double heterojunction, its activity was thoroughly lost after two runs resulting from the continuous photocorrosion. This work provides a valuable insight for preparing efficient semiconductor-metal photocatalysts.

Unveiling the Modification of Esterase-like Activity of Serum Albumin by Nanoplastics and Their Cocontaminants.

Nanoplastics and other cocontaminants have raised concerns due to their widespread presence in the environment and their potential to enter the food chain. The harmful effects of these particles depend on various factors, such as nanoparticle size, shape, surface charge, and the nature of the cocontaminants involved. On entering the human body, human serum albumin (HSA) molecules bind and transport these particles in the blood system. The esterase-like activity of HSA, which plays a role in metabolizing drug/toxic compounds, was taken as a representative to portray the effects of these particles on HSA. Polystyrene nanoplastics (PSNPs) with different surface functionalization (plain (PS), amine (PS-NH2), and carboxy (PS-COOH)), different sizes (100 and 500 nm), and PS with cocontaminant metformin hydrochloride (Met-HCl), a widely used antidiabetic drug, were investigated in this study. Fluorescence emission spectra of HSA revealed that PS-NH2 exhibits a greater effect on protein conformation, smaller NPs have a greater influence on protein structure than larger NPs, and Met-HCl lowers PSNPs' affinity for HSA by coating the surface of the NPs, which may result in direct NP distribution to the drug's target organs and toxicity. Circular dichroism spectra also supported these results in terms of secondary structural changes. Esterase activity of HSA was inhibited by all the particles (except Met-HCl) by competitive inhibition as concluded from constant Vmax and increasing Km. Greater reduction in enzyme activity was observed for PS-NH2 among functionalizations and for 100 nm PS among sizes. Furthermore, Met-HCl lowers the inhibitory impact of PSNPs on HSA since the drug binds weakly to HSA, and so they can serve as a vector delivering PSNPs to their target organs, resulting in serious implications.

Novel P-doping-tuned Pd nanoflowers/S,N-GQDs photo-electrocatalyst for high-efficient ethylene glycol oxidation

Traditional photo-electcatalyst structures of small noble metal nanoparticles assembling into large-scale photoactive semiconductors still suffer from agglomeration of noble metal nanoparticles, insufficient charge transfer, undesirable photoresponse ability that restricted the photo-electrocatalytic performance. To this end, a novel design strategy is proposed in this work, namely integrating small-scale photoactive materials (doped graphene quantum dots, S,N-GQDs) with large-sized noble metal (PdP) nanoflowers to form novel photo-electrocatalysts for high-efficient alcohol oxidation reaction. As expected, superior electrocatalytic performance of PdP/S,N-GQDs for ethylene glycol oxidation is acquired, thanks to the nanoflower structure with larger specific surface area and abundant active sites. Furthermore, nonmetal P are demonstrated, especially optimizing the adsorption strength, enhancing the interfacial contact, reducing metal agglomeration, ensuring uniform and efficient doping of S,N-GQDs, and ultimately significantly boost the catalytic activity of photo-electrocatalysts.

Mesoporous bioactive glass nanoparticles with biomineralization activity for surgical hemorrhage control

ABSTRACTBioactive glass nanoparticles (BGNs) are good bioactive materials for clinical treatment because of their unique composition and silica-oxygen network structure. Herein, we designed and reported a monodisperse mesoporous bioactive glass nanoparticle with biomineralization activity for surgical hemorrhage control. The results indicated that the BGNs have excellent biomineralization ability. In vivo and in vitro hemostasis studies suggested that BGNs have superior hemostatic properties to GZ (gauze) and GS (commercial gelatin sponge) and validated in vitro thrombosis, platelet adhesion, cytocompatibility and blood compatibility. The particles activated both endogenous and exogenous physiological coagulation pathways and could activate platelets and release Ca2+ to participate in the clotting pathway. Besides, the BGNs have good biocompatibility in vivo. These findings demonstrated that the potential of small diameter mesoporous bioactive glass nanoparticles is likely useful for bleeding control as potential hemostatic agents.

Thermal decomposition of acetylacetonates for highly reproducible synthesis of M-ferrite (Mn, Co and Zn) nanoparticles with tunable magnetic properties

In this work, we evaluated two synthetic approaches for the synthesis of M-ferrites nanoparticles, where M = Mn, Co, Zn with desired stoichiometric composition. As a starting point, thermal decomposition of acetylacetonates in benzyl alcohol and benzyl ether with oleic acid was chosen. Both of these approaches are widely used for the preparation of iron oxide nanoparticles; however, the synthesis of M-ferrites nanoparticles using these approaches is not well described. We have studied the influence of the nature of the solvent and surfactant on the quality of obtained ferrites (stoichiometric M:Fe ratio, structural phase analysis, morphology and core size of nanoparticles). It was shown that the chemical structure of solvent and presence of oleic acid plays a key role in controlling the nanoparticles stoichiometry. When benzyl alcohol was used as solvent, M-ferrites nanoparticles with diameters ranging from 3 to 5 nm were obtained, whereas of the benzyl ether with oleic acid resulted in formation of nanoparticles with diameters ranging from 7 to 9 nm. Moreover, only thermal decomposition of M acetylacetonates in benzyl alcohol was successful in obtaining M-ferrites nanoparticles with desired stoichiometry and high reproducibility M:Fe = 1:2 ± 0.1). In addition, magnetic properties of obtained nanoparticles have been studied at room temperature and their dependence on M:Fe ratio (1:2, 1:6, 1:10) was shown. The results show a superparamagnetic behavior for all synthesized samples and high magnetization values from 19.7 to 99.3 A•m2•kg−1. The maximum values of magnetization of M-ferrites samples are quite high for such small nanoparticles, which are closely related to their high crystallinity.

Tuneable Plasmonic Resonances Of A Dynamic Thin Film Of Ultrasmall Nanocrystals Modified In the Anti-Galvanic Reduction Process.

Ultrasmall gold nanoparticles (NPs) have revolutionized nanotechnology as they are an excellent starting substrate for the synthesis of organic-inorganic hybrid materials with photonic or energy conversion applications, often with a responsive nature. However, ultrasmall NPs do not sustain plasmonic resonances, preventing their use in plasmon-related applications. In the presented work, we show a method of chemical modification of ultrasmall gold nanoparticles in order to fabricate dynamically controlled plasmonic thin films. For this purpose, we used the Anti-Galvanic Reduction process (AGR) to modify the surface of small gold nanoparticles, inducing plasmonic properties without notable size increases. Au@Ag NPs are then modified with liquid crystal-like organic ligands. The obtained NPs can assemble into densely packed films with long-range order and temperature-dependent structural properties. Namely, we detect two, fully reversible phase transitions between the hexagonal and cubic symmetries. The combination of AGR and organic surface modifications enabled us to demonstrate the possibility of managing plasmonic properties in the thin film of ~2 nm diameter metallic NPs.