Aggregation Of Nanoparticles Research Articles

Solvent Choice during Flow Assembly of Photocross-Linked Single-Chain Nanoparticles and Micelles Affects Cellular Uptake.

Polymeric micelles have widely been used as drug delivery carriers, and recently, single-chain nanoparticles (SCNPs) emerged as potential, smaller-sized, alternatives. In this work, we are comparing both NPs side by side and evaluate their ability to be internalized by breast cancer cells (MCF-7) and macrophages (RAW 264.7). To be able to generate these NPs on demand, the polymers were assembled by flow, followed by the stabilization of the structures by photocross-linking using blue light. The central aim of this work is to evaluate how the type of solvent affects self-assembly and ultimately the structure of the final NP. Therefore, a library of copolymers with different sequences, including block copolymers (AB, ABA, BAB), and statistical copolymers (rAB and rAC) was synthesized using PET-RAFT with A denoting poly(ethylene glycol) methyl ether acrylate (PEGMEA), B as 2-hydroxyethyl acrylate (HEA), and C as 4-hydroxybutyl acrylate (HBA). The polymers were conjugated with a quinoline derivative to enable the formation of cross-linked structures by photocross-linking during flow assembly. Using water as the dispersant for photocross-linking led to the preassembly of these amphiphilic polymers into compact SCNPs and cross-linked micelles, resulting in a quick photoreaction. In contrast, acetonitrile led to fully dissolved polymers but a low rate of the photoreaction. These intramolecularly cross-linked polymers were then placed in water to result in more dynamic micelles and looser SCNPs. Small-angle X-ray scattering (SAXS), dynamic light scattering (DLS), and size exclusion chromatography (SEC) coupled with a viscosity detector show that cross-linking in acetonitrile results in better-defined NPs with a shell rich in PEGMEA. Cross-linking in acetonitrile led to NPs with significantly higher cellular uptake. Interestingly, passive transport was identified as the main pathway for the delivery of our NPs on MCF-7 cells, confirmed by the uptake of NPs on cells treated with inhibitors and by red blood cells. This work underscored the importance of the polymer precursor's structure and the choice of solvent during intramolecular cross-linking in determining the drug delivery efficiency and biological behavior of SCNPs.

Nanobody-Induced Aggregation of Gold Nanoparticles: A Mix-and-Read Strategy for the Rapid Detection of Cronobacter sakazakii.

Protein-nanoparticle interactions play a crucial role in both biomedical applications and the biosafety assessment of nanomaterials. Here, we found that nanobodies can induce citrate-capped gold nanoparticles (AuNPs) to aggregate into large clusters. Subsequently, we explored the mechanism behind this aggregation and proposed the "gold nucleation mechanism" to explain this phenomenon. Building on this observation, we developed a one-step label-free colorimetric method based on nanobody-induced AuNP aggregation. When nanobodies bind to target bacteria, spatial hindrance occurs, preventing further AuNPs aggregation. This alteration in surface plasmon resonance properties results in visible color changes. As an example, we present a simple and sensitive "mix-and-read" chromogenic immunosensor for Cronobacter sakazakii (C. sakazakii). The experiment can be completed within 20 min, with a visual detection limit of 103 CFU/mL and a quantitative detection limit of 136 CFU/mL. Importantly, our method exhibits no cross-reactivity with other bacterial species. This strategy harnesses the excellent properties of nanobodies and the optical characteristics of AuNPs for direct and rapid detection of foodborne pathogen.

A Fentanyl Hapten‐Displaying Lipid Nanoparticle Vaccine that Non‐Covalently Encapsulates a TLR7/8 Agonist and T‐helper Epitope Induces Protective Anti‐Fentanyl Immunity

Opioid use disorder ‐ particularly involving fentanyl ‐ has precipitated a public health crisis characterized by a significant increase in addiction and overdose‐related deaths. Fentanyl‐specific immunotherapy, which aims at inducing fentanyl‐specific antibodies capable of binding fentanyl molecules in the bloodstream, preventing their entry in the central nervous system, is therefore gaining momentum. Conventional opioid designs rely on the covalent conjugation of fentanyl analogues to immunogenic carrier proteins that hold the inherent capacity of mounting immunodominant responses. Here, we present an alternative fentanyl vaccine design that utilizes a non‐covalent assembly of lipid nanoparticles (LNPs) to deliver fentanyl haptens in conjunction with a CD4+ T‐helper peptide epitope and an imidazoquinoline TLR7/8 agonist. Our results demonstrate that a single intramuscular administration of the LNP‐based nanovaccine elicits fentanyl‐specific antibodies, significantly mitigating the effects of opioid overdose in preclinical mouse models. Furthermore, we analyzed the immunobiological behavior of the vaccine in vivo in mouse models, providing evidence that covalent attachment of a fentanyl hapten to a carrier proteins or peptide epitope is not necessary for inducing an effective immune response. However, co‐delivery ‐ specifically, the physical assembly of all immune cues into an LNP ‐ remains essential for inducing hapten‐specific immunity.

A Fentanyl Hapten-Displaying Lipid Nanoparticle Vaccine that Non-Covalently Encapsulates a TLR7/8 Agonist and T-helper Epitope Induces Protective Anti-Fentanyl Immunity.

Opioid use disorder - particularly involving fentanyl - has precipitated a public health crisis characterized by a significant increase in addiction and overdose-related deaths. Fentanyl-specific immunotherapy, which aims at inducingfentanyl-specificantibodies capable of binding fentanyl molecules in the bloodstream, preventing their entry in the central nervous system, is therefore gaining momentum.Conventional opioid designsrely on the covalent conjugation of fentanyl analogues to immunogenic carrier proteins that hold the inherent capacity of mounting immunodominant responses. Here, we present an alternative fentanyl vaccine design that utilizes a non-covalent assembly of lipid nanoparticles (LNPs) to deliver fentanyl haptens in conjunction with a CD4+T-helper peptide epitope and an imidazoquinoline TLR7/8 agonist. Our results demonstrate that a single intramuscular administration of the LNP-based nanovaccine elicits fentanyl-specific antibodies, significantly mitigating the effects of opioid overdose in preclinical mouse models. Furthermore, we analyzed the immunobiological behavior of the vaccine in vivo in mouse models, providing evidence that covalent attachment of a fentanyl hapten to a carrier proteins or peptide epitope is not necessary for inducing an effective immune response. However, co-delivery - specifically, the physical assembly of all immune cues into an LNP - remains essential for inducing hapten-specific immunity.

Macroscopic Room-Temperature Magnetoelectricity in Piezoelectric (Core)-Ferrimagnetic (Shell) Nanocomposites.

The magnetoelectric (ME) effect, which involves the interaction of magnetic and electric fields within a material, has a significant potential for various applications. Our study addresses the limitations of conventional magnetostriction-based ME materials by demonstrating an alternative approach that achieves substantial ME effects in core-shell-type nanocomposites at room temperature. By synthesizing ferrimagnetic Fe3O4 nanoparticles onto piezoelectric poly(vinylidene fluoride) (PVDF) particles, we identified a distinct ME mechanism. In magnetorheological (MR) fluids, the magnetic-field-induced aggregation of Fe3O4 nanoparticles, combined with the piezoelectricity of PVDF, leads to a pronounced ME effect, significantly enhancing the performance and stability of MR fluids. This research highlights a crucial observation of distinct ME effects, which could suggest potential pathways for advancements in practical applications including microfluidics, vibration dampers, tactile technologies, and biomedical and bioengineering fields.

Recent Updates on Diverse Nanoparticles and Nanostructures in Therapeutic and Diagnostic Applications with Special Focus on Smart Protein Nanoparticles: A Review.

Nanomedicine enables advanced therapeutics, diagnostics, and predictive analysis, enhancing treatment outcomes and patient care. The choices and development of high-quality organic nanoparticles with relatively lower toxicity are important for achieving advanced medical goals. Among organic molecules, proteins have been prospected as smart candidates to revolutionize nanomedicine due to their inherent fascinating features. The advent of protein nanoarchitectures, which explore the biomolecular corona, offers new insights into their efficient tissue penetration and therapeutic potential. This review examines various animal- and plant-based protein nanoparticles, highlighting their source, activity, products, and unique biomedical applications in regenerative medicine, targeted therapies, gene and drug delivery, antimicrobial activity, bioimaging, immunological adjuvants, etc. It provides an extensive discussion on recent applications of protein nanoparticles across diverse biomedical fields as well as the evolving landscape of other nanoproducts and nanodevices for sensitive medical procedures. Furthermore, this review introduces different preparation technologies of protein nanoparticles, emphasizing how their design and construction significantly influence loading capacity, stability, and targeting effects. Additionally, we delve into the construction of different user-friendly multifunctional modular bioarchitectures by the assembly of protein nanoparticles (PNPs), marking a significant breakthrough in therapies. This review also considers the challenges of synthetic nanomaterials and the emergence of natural alternatives, which provides insights into protein nanoparticle research.

Lignin-Based N-Carbon Dots Anchoring NiCo2S4/Graphene Hydrogel Exhibits Excellent Performance as Anodes for Hybrid Supercapacitor

A NiCo2S4/N-CDs/RGO ternary composite hydrogel was prepared via a one-step hydrothermal method, utilizing lignin-based nitrogen-doped carbon dots as a bridge connecting NiCo2S4 and graphene. The specific capacitance of NiCo2S4/N-CDs/RGO significantly outperforms that of the GH and NiCo2S4/RGO electrodes, achieving 1050 F g−1. The 3D mesh porous hydrogel structure mitigates NiCo2S4 nanoparticle aggregation, providing a larger specific surface area for enhanced charge storage. The abundant functional groups of N-CDs interact with Ni (II) and Co (III) cations, favoring NiCo2S4 particle synthesis. Additionally, an assembled solid-state asymmetric supercapacitor employing NiCo2S4/N-CDs/RGO as the positive electrode exhibited excellent energy density (68.4 Wh kg−1) and cycle stability (82% capacitance retention after 10,000 constant current charge–discharge cycles).

Iron phosphide nanoparticles anchored on 3D nitrogen-doped graphene as an efficient electrocatalysts for hydrogen evolution reaction in alkaline media

Electrocatalysts play a crucial role in hydrogen evolution reaction (HER), facilitating a clean and sustainable generation of hydrogen energy. To promote the HER process, it is imperative to employ highly efficient, stable, and cost-effective electrocatalysts. This research focuses on the design of iron phosphide nanoparticles anchored onto a porous three-dimensional nitrogen-doped graphene (FeP@3DNG). The porous framework of 3DNG serves a multifaceted purpose: it prevents the aggregation of FeP nanoparticles during phosphidation, safeguards the FeP electrocatalyst from oxidation during the HER, and simultaneously enhances electrical conductivity and stability. Notably, the FeP@3DNG nanocomposite demonstrated the efficient activity and highest HER activity with an overpotential of 76 mV to achieve 10 mA cm−2 and a small Tafel slope of 40.2 mV dec−1 as well as good long-term durability for 20 h in 1.0 M KOH solution. The high performance of the FeP@3DNG nanocomposite can be primarily corresponded to the synergistic effects of the highly active of FeP nanoparticles and advantages of porous three-dimensional graphene with excellent electrocatalytic activity, high specific surface area, and chemical stability, thus, resulting in the improvement the overall electrocatalytic activity.

Self-Adaptive Magnetic Liquid Metal Microrobots Capable of Crossing Biological Barriers and Wireless Neuromodulation.

Magnetic liquid-bodied microrobots (MRs) possess nearly infinite shape adaptivity. However, they currently confront the risk of structure instability/crushes during shape-morphing in tiny biological environments. This article reports that magnetic liquid metal (LM) MRs (LMMRs) show high structure stability and robust magnetic maneuverability. In this protocol, Fe nanoparticles are encapsulated inside less-than-10-μm LM microdroplets by establishing interfacial chemical potential barriers, yielding LMMRs. Their robust magnetic maneuverability originates from the magnetically controlled assembly of Fe nanoparticles inside LM and distinct liquid-solid interaction. With the self-adaptive shape-recovering capabilities even after 50% deformation, LMMRs can implement vertical climbing over walls up to 400% of its body length and traverse channels with the size of its two-thirds. The in vitro and in vivo experiments have both verified the effective magneto-mechanical stimulation of LMMRs upon neurons after their shape-adaptive crossing the blood-brain barrier under a driven magnetic field. Our work provides a promising strategy for wireless therapies with MRs by safely and effectively overcoming biological barriers.

Oxidative Dissolution and the Aggregation of Silver Nanoparticles in Drinking and Natural Waters: The Influence of the Medium on the Process Development.

Currently, there are quite a few data on the ways silver nanoparticles get into the aquatic environment, on their subsequent dissolution in water, and on the release of toxic Ag+ ions. Differences in the experimental conditions hinder the determination of the basic regularities of this process. In this study, the stages of oxidative dissolution of AgNPs were studied, starting from the formation of silver hydrosol in deaerated solution, the reaction of silver with oxygen and with drinking and natural waters, the analysis of intermediate species of the oxidized colloidal particles, and the subsequent particle aggregation and precipitation, by optical spectroscopy, DLS, TEM, STEM, and EDX. In the presence of oxygen, silver nanoparticles undergo oxidative dissolution, which gives Ag+ ions and results in the subsequent aggregation of nanoparticles. The carbonate hydrosol loses stability when mixed with waters of various origin. This is due to the destruction of the electric double layer, which is caused by an increase in the solution's ionic strength and the neutralization of the charge of the metal core. The environmental hazard of the silver nanoparticle hydrosol would noticeably change and/or decrease when the nanoparticles get into natural waters because of their fast precipitation and because the major part of released Ag+ ions form poorly soluble salts with ions present in water.

Hairygami: Analysis of DNA Nanostructures' Conformational Change Driven by Functionalizable Overhangs.

DNA origami is a widely used method to construct nanostructures by self-assembling designed DNA strands. These structures are often used as "pegboards" for templated assembly of proteins, gold nanoparticles, aptamers, and other molecules, with applications ranging from therapeutics and diagnostics to plasmonics and photonics. Imaging these structures using atomic force microscopy (AFM) or transmission electron microscope (TEM) does not capture their full conformation ensemble as they only show their shape flattened on a surface. However, certain conformations of the nanostructure can position guest molecules into distances unaccounted for in their intended design, thus leading to spurious interactions between guest molecules that are designed to be separated. Here, we use molecular dynamics simulations to capture a conformational ensemble of two-dimensional (2D) DNA origami tiles and show that introducing single-stranded overhangs, which are typically used for functionalization of the origami with guest molecules, induces a curvature of the tile structure in the bulk. We show that the shape deformation is of entropic origin, with implications for the design of robust DNA origami breadboards as well as a potential approach to modulate structure shape by introducing overhangs. We then verify experimentally that the DNA overhangs introduce curvature into the DNA origami tiles under divalent as well as monovalent salt buffer conditions. We further experimentally verify that DNA origami functionalized with attached proteins also experiences such induced curvature. We provide the developed simulation code implementing the enhanced sampling to characterize the conformational space of DNA origami as open source software.

Numerical analysis on the fate and transport of TiO2 nanoparticles in fractured porous media: Addressing intrinsic heterogeneities in sorptive mass transfer

The aggregation and slow migration of nanoparticles in aqueous media have caused serious concerns about their fate and impacts in the subsurface environment. Anthropogenic release and distribution of TiO2 nanoparticles (TNP) have immense potential for surface adsorption, occlusion, impregnation, bioaccumulation, and phase partition into various environmental compartments, and the actual risks in their interactions are still unknown. In an attempt to realize the extent of source zone migration of TNP in a fracture-skin-matrix (F-S-M) medium, a numerical model is developed and analyzed for sensitivity of certain features of the flow field. In addition, the sorptive mass transfer is simulated under four characteristic scenarios with varying assumptions pertaining to the intrinsic heterogeneities. The simulation results highlight the non-selective regulatory role of the skin in providing temporary interfacial space for reversible adsorption between the fracture and the matrix as well as in retarding the desorption rate. A preferential detachment of TNP is observed to be favored by the enhanced properties of skin due to the similarity in diffusion and dispersion coefficients. Out of the four scenarios, the two-site model and two-step model simulated the dynamic pore-filling features of adsorption pertaining to the heterogeneities in TNP and F-S-M characteristics. The results demonstrate that the proposed numerical could fairly detect the transition between local equilibrium and dynamic adsorption-desorption cycles that would eventually determine the mass transfer limitations and the extent of elution of TNP along the flow.

Nanoscopically Confined 1,4-Polybutadiene Melts: Exploring Confinement by Alumina Nanorod and Nanopore Systems.

We present molecular dynamics simulations of a chemically realistic model of 1,4-polybutadiene (PBD) in contact with curved alumina surfaces. We contrast the behavior of PBD infiltrated into alumina pores with a curvature radius of about three times the radius of gyration of the chains to its behavior next to a melt dispersed alumina rod of equal absolute curvature. These confinement types represent situations occurring in polymer melts loaded with nanoparticles due to nanoparticle aggregation. While there are observable differences in structure and dynamics due to the different types of geometric confinement, the main effects stem from the strong attraction of PBD to the alumina surfaces. This strong attraction leads to a deformation of the chains in contact to the surfaces. We focus on temperatures well above the bulk glass transition temperature, but even at these high temperatures, the layers next to the alumina surfaces show glass-like relaxation behavior. We analyze the signature of this glassy behavior for neutron scattering or nuclear magnetic resonances experiments.

Multifunctional self-assembled nanoparticles serving as the signal labels of fluorescent immunoassays

Nanolabels composed of multiple small molecules have shown great potential as the signal tags of immunoassays. However, their practical applications are limited by the complex preparation and modification procedures. This study proposed the design of multifunctional nanoparticles as the signal labels of fluorescent immunoassays, which were prepared by the self-assembly of biotinylated pyrene-phenylalanine (bio-PyF) monomers. The recognition elements of biotin moieties on the nanoparticles enabled their attachment on the sensor surface through streptavidin–biotin interactions. The tetrameric streptavidin proteins serving as the crosslinkers induced the in-situ assembly of bio-PyF nanoparticles (bio-PyFNPs) into network architectures on the sensor interface, thus achieving the second signal amplification. The captured nanoparticles were disrupted into a large number of signal reporters with pyrene tags under external surfactant stimulus. The inherent fluorescent property of pyrene allowed for the detection of targets with high simplicity and sensitivity. The analytical performances of the immunoassays were evaluated by determining alpha-fetoprotein (AFP) in buffer and serum samples, achieving a detection limit down to 0.5 pg/mL. This method offers a simple, sensitive, and selective alternative to conventional enzyme-linked immunosorbent assays for clinical diagnosis. The proposed strategy holds great promise for the development of novel signal labels and self-assembly-based biosensors.

Synthesis of metal nanoparticles on graphene oxide and antibacterial properties.

Pathogen-induced infections and the rise of antibiotic-resistant bacteria, such as Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), pose significant global health challenges, emphasizing the need for new antimicrobial strategies. In this study, we synthesized graphene oxide (GO)-based composites functionalized with silver nanoparticles (AgNPs) and copper nanoparticles (CuNPs) as potential alternatives to traditional antibiotics. The objective is to assess the antibacterial properties of these composites and explore their efficacy against E. coli and S. aureus, two common bacterial pathogens. The composites are prepared using eco-friendly and conventional methods to ensure effective nanoparticle attachment to the GO surface. Structural and morphological characteristics are confirmed through SEM, AFM, EDS, XRD, UV-vis, FTIR, and Raman spectroscopy. The antibacterial efficacy of the composites is tested through disk diffusion assays, colony-forming unit (CFU) counts, and turbidimetry analysis, with an emphasis on understanding the effects of different nanoparticle concentrations. The results demonstrated a dose-dependent antibacterial effect, with GO/AgNP-1 showing superior antibacterial activity over GO/AgNP-2, particularly at lower concentrations (32.0μg/mL and 62.5μg/mL). The GO/CuNP composite also exhibited significant antibacterial properties, with optimal performance at 62.5μg/mL for both bacterial strains. Turbidimetry analysis confirmed the inhibition of bacterial growth, especially at moderate concentrations, although slight nanoparticle aggregation at higher doses reduced efficacy. Lastly, both GO/AgNP and GO/CuNP composites demonstrated significant antibacterial potential. The results emphasize the need to fine-tune nanoparticle concentration and refine synthesis techniques to improve their efficacy, positioning these composites as strong contenders for antimicrobial use.

RNA Nanotechnology for Codelivering High-Payload Nucleoside Analogs to Cancer with a Synergetic Effect.

Nucleoside analogs are potent inhibitors for cancer treatment, but the main obstacles to their application in humans are their toxicity, nonspecificity, and lack of targeted delivery tools. Here, we report the use of RNA four-way junctions (4WJs) to deliver two nucleoside analogs, floxuridine (FUDR) and gemcitabine (GEM), with high payloads through routine and simple solid-state RNA synthesis and nanoparticle assembly. The design of RNA nanotechnology for the co-delivery of nucleoside analogs and the chemotherapeutic drug paclitaxel (PTX) resulted in synergistic effects and high efficacy in the treatment of Triple-Negative Breast Cancer (TNBC). The 4WJ-drug complexes were confirmed to have efficient tumor spontaneous targeting and no toxicity because the motility of RNA nanoparticles has been previously shown to enable these RNA-drug complexes to spontaneously accumulate in tumor blood vessels. The negative charge of RNA enables those RNA complexes that are not targeted to tumor vasculature to circulate in the blood and enter the urine through the kidney glomerulus, without accumulating in organs, therefore being nontoxic. Drug incorporation into RNA 4WJ can be precisely controlled with a defined loading amount, location, and ratio. The incorporation of nucleoside analogs into 4WJ only requires one step using nucleoside analogue phosphoramidites during solid-phase RNA synthesis, without the need for additional conjugation and purification processes.

Manganese Oxide-Doped Hierarchical Porous Carbon Derived from Tea Leaf Waste for High-Performance Supercapacitors.

Hierarchical porous carbon derived from discarded biomass for energy storage materials has attracted increasing research attention due to its cost-effectiveness, ease of fabrication, environmental protection, and sustainability. Brewed tea leaves are rich in heteroatoms that are beneficial to capacitive energy storage behavior. Therefore, we synthesized high electrochemical performance carbon-based composites from Tie guan yin tea leaf waste using a facile procedure comprising hydrothermal, chemical activation, and calcination processes. In particular, potassium permanganate (KMnO4) was incorporated into the potassium hydroxide (KOH) activation agent; therefore, during the activation process, KOH continued to erode the biomass precursor, producing abundant pores, and KMnO4 synchronously underwent a redox reaction to form MnO nanoparticles and anchor on the porous carbon through chemical bonding. MnO nanoparticles provided additional pseudocapacitive charge storage capabilities through redox reactions. The results show that the amount of MnO produced is proportional to the amount of KMnO4 incorporated. However, the specific surface area of the composite material decreases with the incorporated amount of KMnO4 due to the accumulation and aggregation of MnO nanoparticles, thereby even blocking some micropores. Optimization of MnO nanocrystal loading can promote the crystallinity and graphitization degree of carbonaceous materials. The specimen prepared with a weight ratio of KMnO4 to hydrochar of 0.02 exhibited a high capacitance of 337 F/g, an increase of 70%, owing to the synergistic effect between the Tie guan yin tea leaf-derived activated carbon and MnO nanoparticles. With this facile preparation method and the resulting high electrochemical performance, the development of manganese oxide/carbon composites derived from tea leaf biomass is expected to become a promising candidate as an energy storage material for supercapacitors.

Development of enzyme-based biosensor for residual detection of organophosphate pesticides using functionalized nanocellulose-modified silver nanoparticles

Excessive use of pesticides to satisfy the demand of a rapidly increasing population has posed numerous problems for human health and the environment. Therefore, we developed a nanocomposite comprised of rice husk-derived dialdehyde nanocellulose capped silver nanoparticles (AgNP@DANC) as an efficient immobilizing material for acetylcholinesterase (AChE) to develop a novel biosensor. This revolutionary enzyme-based biosensor was used for the rapid detection of organophosphate pesticides (OPs) using chlorpyrifos (CPF) and malathion (MLT) as representative pesticides in food stuffs. The detection of OPs is based on the inhibition of the catalytic activity of AChE in the presence of CPF and MLT coupled with the aggregation of silver nanoparticles (AgNPs) due to thiocholine that can be analyzed for rapid screening. The developed biosensor for CPF and MLT shows ultrasensitive behaviour over a linear range of 1 × 10−3 to 1 × 10-19 M and 1 × 10−3 to 1 × 10−17 M, respectively. Further, the sensitivity of the developed biosensor was also studied for real spiked samples. The developed biosensor shows great potential and sensitivity; thus, it could be a promising biosensor for the rapid and on-site detection of many OPs.

Evaluation of long-term stability of L-asparaginase encapsulated PLL-g-PEG nanoparticles in solution to aid in therapeutic delivery

Abstract L-asparaginase (L-ASNase) is a therapeutic enzyme that is widely used for the treatment of hematopoietic diseases such as acute lymphoblastic leukemia and lymphomas. L-ASNase destroys asparagine dependent tumors by degrading circulating L-asparagine and thereby destroying malignant cells. As a protein drug, L-ASNase carries a few inherent drawbacks including short circulating half-life, low stability, and low catalytic activity under physiological conditions. Moreover, due to the bacterial origin of L-ASNase used in treatments, there have been reports with high frequency of hypersensitivity reactions in patients. The use of this drug in adult cancer populations has largely been hindered not only due to its immunological side effects but also due to non-immunogenic toxicities such as pancreatitis, liver toxicities, coagulopathy, and neurotoxicity. Therefore, it is vital to find new methods to decrease its immunogenic/toxicity profile while increasing the stability and half-life. The purpose of this study is to achieve a new L-ASNase polymer nanocarrier to improve stability of the enzyme while masking it from the immune system of the host. We designed and characterized a nanoparticle (NP) where a poly-L-lysine-grafted-poly(ethylene) glycol co-polymer was used to encapsulate L-ASNase. The primary focus of the study was to evaluate the stability and encapsulation efficiency of this NP construct over time. There was no aggregation of NPs observed during the study period of 6 months in solution and NPs had a 0.436 mV surface charge. L-ASNase NPs showed a percent asparaginase activity of 31% compared to free L-ASNase. Under physiological conditions NPs were found to be intact and retained the encapsulated proteins for up to 6 months in solution. Together, these results demonstrate that L-ASNase loaded PLL-g-PEG NPs may serve as a fundamental platform to design nanocarriers to prolong stability in solution.

Oxidation of Toluene over the Pt-Embedded Mesoporous CeO2 Hollow Nanospheres with Advanced Catalytic Performances.

In this study, the novel Pt-embedded mesoporous CeO2 hollow nanospheres (Pt-MS-CeO2-H) with varying Pt contents (0.5-3.0 wt %) were facilely prepared. The Pt nanoparticles were one-pot embedded within the mesoporous shell of Pt-MS-CeO2-H and assisted with the reduction Ostwald ripening process. The traditional preparation methods often face challenges, such as the uneven distribution or aggregation of nanoparticles, as well as difficulty in maintaining high catalytic activity at low Pt content. Compared with the traditional supported Pt/MS-CeO2 catalyst, the embedding strategy facilitated precise control over the position, distribution, and uniformity of Pt nanoparticles within the CeO2 mesoporous shell. Additionally, the encapsulation process of Pt nanoparticles played a pivotal role in generating oxygen vacancies and activating surface chemical adsorption of oxygen. Resultantly, the toluene oxidation performances of 1Pt-MS-CeO2-H catalyst showed much lower T90 (171 °C) than 1Pt/MS-CeO2 (311 °C). To elucidate the underlying reasons, in situ diffuse reflectance infrared Fourier transform spectroscopy of toluene oxidation was employed to identify the reaction intermediates and pathways over these catalysts. In summary, the Pt-embedded mesoporous CeO2 hollow nanosphere catalysts were considered as potential candidates when designing high-performance toluene catalytic oxidation catalysts.