Corona Layer Research Articles

Cryogenic electron microscopy reveals morphologically distinct subtypes of extracellular vesicles among porcine ejaculate fractions

Seminal plasma (SP) is rich in extracellular vesicles (EVs), which are still poorly studied, especially in livestock species. To better understand their functional role in both spermatozoa and endometrial epithelial cells, proper characterization of EVs is an essential step. The objective was to phenotypically characterize porcine seminal EVs (sEVs) using cryogenic electron microscopy (cryo-EM), which allows visualization of EVs in their native state. Porcine ejaculates are released in fractions, each containing SP from different source. This allows characterization sEVs released from various male reproductive tissues. Two experiments were performed, the first with SP from the entire ejaculate (n:6) and the second with SP from three ejaculate fractions (n:15): the first 10 mL of the sperm-rich ejaculate fraction (SRF-P1) with SP mainly from the epididymis, the remainder of the SRF (SRF-P2) with SP mainly from the prostate, and the post-SRF with SP mainly from the seminal vesicles. The sEVs were isolated by size exclusion chromatography and 1840 cryo-EM sEV images were acquired using a Jeol-JEM-2200FS/CR-EM. The size, electron density, complexity, and peripheral corona layer were measured in each sEV using the ImageJ software. The first experiment showed that sEVs were structurally and morphologically heterogeneous, although most (83.1%) were small (less than 200 nm), rounded, and poorly electrodense, and some have a peripheral coronal layer. There were also larger sEVs (16.9%) that were irregularly shaped, more electrodense, and few with a peripheral coronal layer. The second experiment showed that small sEVs were more common in SRF-P1 and SRF-P2, indicating that they originated mainly from the epididymis and prostate. Large sEVs were more abundant in post-SRF, indicating that they originated mainly from seminal vesicles. Porcine sEVs are structurally and morphologically heterogeneous. This would be explained by the diversity of reproductive organs of origin.

Harnessing barley grains for green synthesis of gold and silver nanoparticles with antibacterial potential

The continuous evolution and significance of green resources-based nanomaterials have spurred the exploration of sustainable sources for nanoparticle production. Green synthesis routes offer eco-friendly methodologies, ensuring nanoparticle stability and monodispersity, enhancing their efficiency for various applications. Notably, the thick biological corona layer surrounding nanoparticles (NPs) synthesized through green routes contributes to their unique properties. Consequently, there has been a surge in the development of NPs synthesis methods utilizing medicinal plants and diverse agricultural and waste resources. This study highlights the sustainable potential of barley grains for the synthesis of gold nanoparticles (Barley-AuNPs) and silver nanoparticles (Barley-AgNPs) as an environmentally friendly alternative, followed by NPs characterizations and their application against pathogenic bacteria: Escherichia coli UTI 89 and Pseudomonas aeruginosa PAO1. The rapid synthesis of Barley-AuNPs within 20 min and Barley-AgNPs within 30 min at 90 °C underscores the efficiency of barley as a green precursor. Characterization through advanced techniques, including SEM, TEM, EDS, AFM, DLS, FT-IR, MALDI-TOF, and sp-ICPMS, reveals the 20–25 nm size for Barley-AuNPs, while Barley-AgNPs demonstrate 2–10 nm size with spherical monodispersity. A notable contribution lies in the stability of these NPs over extended periods, attributed to a thick biological corona layer. This corona layer, which enhances stability, also influences the antimicrobial activity of Barley-AgNPs, presenting an intriguing trade-off. The antimicrobial investigations highlight the significant potential of Barley-AgNPs, with distinct minimum bactericidal concentrations (MBC) against P. aeruginosa and E. coli at 8 µg/mL. Overall, this research pioneers the use of barley grains for nanoparticle synthesis and unveils these nanoparticles' unique characteristics and potential antibacterial applications, contributing to the evolving landscape of sustainable nanotechnology.Graphic

Anion Architecture Controls Structure and Electroresponsivity of Anhalogenous Ionic Liquids in a Sustainable Fluid.

Three nonhalogenated ionic liquids (ILs) dissolved in 2-ethylhexyl laurate (2-EHL), a biodegradable oil, are investigated in terms of their bulk and electro-interfacial nanoscale structures using small-angle neutron scattering (SANS) and neutron reflectivity (NR). The ILs share the same trihexyl(tetradecyl)phosphonium ([P6,6,6,14]+) cation paired with different anions, bis(mandelato)borate ([BMB]-), bis(oxalato)borate ([BOB]-), and bis(salicylato)borate ([BScB]-). SANS shows a high aspect ratio tubular self-assembly structure characterized by an IL core of alternating cations and anions with a 2-EHL-rich shell or corona in the bulk, the geometry of which depends upon the anion structure and concentration. NR also reveals a solvent-rich interfacial corona layer. Their electro-responsive behavior, pertaining to the structuring and composition of the interfacial layers, is also influenced by the anion identity. [P6,6,6,14][BOB] exhibits distinct electroresponsiveness to applied potentials, suggesting an ion exchange behavior from cation-dominated to anion-rich. Conversely, [P6,6,6,14][BMB] and [P6,6,6,14][BScB] demonstrate minimal electroresponses across all studied potentials, related to their different dissociative and diffusive behavior. A mixed system is dominated by the least soluble IL but exhibits an increase in disorder. This work reveals the subtlety of anion architecture in tuning bulk and electro-interfacial properties, offering valuable molecular insights for deploying nonhalogenated ILs as additives in biodegradable lubricants and supercapacitors.

Kinesin-7 CENP-E in tumorigenesis: Chromosome instability, spindle assembly checkpoint, and applications.

Kinesin motors are a large family of molecular motors that walk along microtubules to fulfill many roles in intracellular transport, microtubule organization, and chromosome alignment. Kinesin-7 CENP-E (Centromere protein E) is a chromosome scaffold-associated protein that is located in the corona layer of centromeres, which participates in kinetochore-microtubule attachment, chromosome alignment, and spindle assembly checkpoint. Over the past 3decades, CENP-E has attracted great interest as a promising new mitotic target for cancer therapy and drug development. In this review, we describe expression patterns of CENP-E in multiple tumors and highlight the functions of CENP-E in cancer cell proliferation. We summarize recent advances in structural domains, roles, and functions of CENP-E in cell division. Notably, we describe the dual functions of CENP-E in inhibiting and promoting tumorigenesis. We summarize the mechanisms by which CENP-E affects tumorigenesis through chromosome instability and spindle assembly checkpoints. Finally, we overview and summarize the CENP-E-specific inhibitors, mechanisms of drug resistances and their applications.

Effects of Polyether Amine Canopy Structure on Heavy Metal Ions Adsorption of Magnetic Solvent-Free Nanofluids.

Three Fe3O4 magnetic solvent-free nanofluids with different amine-based coronal layer structures are synthesized and characterized by using magnetic Fe3O4 as the core, silane coupling agent as the corona, and polyether amines with different graft densities and chain lengths as the canopy. The concentration of heavy metal ions after adsorption is measured by atomic absorption spectrometry (AAS) to study the effect of Fe3O4 magnetic solvent-free nanofluids on the adsorption performance of the heavy metal ions lead (Pb(II)) and copper (Cu(II)) in water. The adsorption of Fe3O4 magnetic solvent-free nanofluid was explored by changing external condition factors such as adsorption contact time and pH. Additionally, the adsorption model is established. The magnetic solvent-free nanofluid is separated from water by applying an external magnetic field to the system, and desorption and cyclic adsorption tests are carried out. Based on the adsorption mechanism, the structure design of Fe3O4 magnetic solvent-free nanofluid was optimized to achieve optimal adsorption performance.

Albumin Hydrogel-Coated Mesoporous Silica Nanoparticle as a Carrier of Cationic Porphyrin and Ratiometric Fluorescence pH Sensor.

Here, we report that a mesoporous silica nanoparticle (MSN) coated with a fluoresceine-labeled bovine serum albumin (F-BSA) hydrogel layer works as a temperature-responsive nanocarrier for tetrakis-N-methylpyridyl porphyrin (TMPyP) and as a fluorescence ratiometric pH probe. F-BSA hydrogel-coated MSN containing TMPyP (F-BSA/MSN/TMPyP) was synthesized by thermal gelation of denatured F-BSA on the external surface of MSN. The F-BSA hydrogel layer was composed of an inner hard corona layer and an outer soft layer and was stable under physiological conditions. F-BSA/MSN/TMPyP exhibited temperature-dependent exponential release of TMPyP. In this release profile, the MSN was found to be a suitable host for stable encapsulation of tetracationic TMPyP by electrostatic interactions, and the F-BSA hydrogel layer mediated the diffusion of TMPyP from the MSN pore interior into the solution phase. Increasing temperature promoted partitioning of TMPyP from the pore interior to the F-BSA hydrogel layer, from where it was spontaneously released into the bulk solution phase by cation exchange. F-BSA/MSN/TMPyP also gave a linear ratiometric fluorescence response (1.3 per pH unit) in the pH range from 6.1 to 8.9.

A uniform data processing pipeline enables harmonized nanoparticle protein corona analysis across proteomics core facilities

Protein corona, a layer of biomolecules primarily comprising proteins, forms dynamically on nanoparticles in biological fluids and is crucial for predicting nanomedicine safety and efficacy. The protein composition of the corona layer is typically analyzed using liquid chromatography-mass spectrometry (LC-MS/MS). Our recent study, involving identical samples analyzed by 17 proteomics facilities, highlighted significant data variability, with only 1.8% of proteins consistently identified across these centers. Here, we implement an aggregated database search unifying parameters such as variable modifications, enzyme specificity, number of allowed missed cleavages and a stringent 1% false discovery rate at the protein and peptide levels. Such uniform search dramatically harmonizes the proteomics data, increasing the reproducibility and the percentage of consistency-identified unique proteins across distinct cores. Specifically, out of the 717 quantified proteins, 253 (35.3%) are shared among the top 5 facilities (and 16.2% among top 11 facilities). Furthermore, we note that reduction and alkylation are important steps in protein corona sample processing and as expected, omitting these steps reduces the number of total quantified peptides by around 20%. These findings underscore the need for standardized procedures in protein corona analysis, which is vital for advancing clinical applications of nanoscale biotechnologies.

Multifunctional Polymer Vesicles for Synergistic Antibiotic-Antioxidant Treatment of Bacterial Keratitis.

As an acute ophthalmic infection, bacterial keratitis (BK) can lead to severe visual morbidity, such as corneal perforation, intraocular infection, and permanent corneal opacity, if rapid and effective treatments are not available. In addition to eradicating pathogenic bacteria, protecting corneal tissue from oxidative damage and promoting wound healing by relieving inflammation are equally critical for the efficient treatment of BK. Besides, it is very necessary to improve the bioavailability of drugs by enhancing the ocular surface adhesion and corneal permeability. In this investigation, therefore, a synergistic antibiotic-antioxidant treatment of BK was achieved based on multifunctional block copolymer vesicles, within which ciprofloxacin (CIP) was simultaneously encapsulated during the self-assembly. Due to the phenylboronic acid residues in the corona layer, these vesicles exhibited enhanced muco-adhesion, deep corneal epithelial penetration, and bacteria-targeting, which facilitated the drug delivery to corneal bacterial infection sites. Additionally, the abundant thioether moieties in the hydrophobic membrane enabled the vesicles to both have ROS-scavenging capacity and accelerated CIP release at the inflammatory corneal tissue. In vivo experiments on a mice model demonstrated that the multifunctional polymer vesicles achieved efficient treatment of BK, owing to the enhanced corneal adhesion and penetration, bacteria targeting, ROS-triggered CIP release, and the combined antioxidant-antibiotic therapy. This synergistic strategy holds great potential in the treatment of BK and other diseases associated with bacterial infections.

Protein Corona Formation on Lipid Nanoparticles Negatively Affects the NLRP3 Inflammasome Activation.

The interaction between lipid nanoparticles (LNPs) and serum proteins, giving rise to a unique identification in the form of the protein corona, has been shown to be associated with novel recognition by cell receptors. The presence of the corona enveloping the nanoparticle strongly affects the interplay with immune cells. The immune responses mediated by protein corona can affect nanoparticle toxicity and targeting capabilities. But the intracellular signaling of LNPs after corona formation resulting in the change of nanoparticles' ability to provoke immune responses remains unclear. Therefore, a more systematic and delineated approach must be considered to present the correlation between corona complexes and the shift in nanoparticle immunogenicity. Here, we studied and reported the inhibiting effect of the absorbed proteins on the LNPs on the NLRP3 inflammasome activation, a key intracellular protein complex that modulates several inflammatory responses. Ionizable lipid as a component of LNP was observed to play an important role in modulating the activation of NLRP3 inflammasome in serum-free conditions. However, in the presence of serum proteins, the corona layer on LNPs caused a significant reduction in the inflammasome activation. Reduction in the lysosomal rupture after treatment with corona-LNPs significantly reduced inflammasome activation. Furthermore, a strong reduction of cellular uptake in macrophages after the corona formation was observed. On inspecting the uptake mechanisms in macrophages using transport inhibitors, lipid formulation was found to play a critical role in determining the endocytic pathways for the LNPs in macrophages. This study highlights the need to critically analyze the protein interactions with nanomaterials and their concomitant adaptability with immune cells to evaluate nano-bio surfaces and successfully design nanomaterials for biological applications.

High CO and sulfur tolerant proton exchange membrane fuel cell anodes enabled by “work along both lines” mechanism of 2,6-dihydroxymethyl pyridine molecule blocking layer

Proton exchange membrane fuel cells (PEMFCs) are hindered by their poor tolerance to CO and H2S poisoning. Herein, we report an effective method, via engineering 2,6-dihydroxymethyl pyridine (DhmPy) molecule blocking layers on Pt surface, aiming to save the poisoning issue for PEMFC anode reaction. The PEMFCs assembled by this catalyst produce a power density of 1.18 W cm−2 @ 2.0 A cm−2 and 1.32 W cm−2 @ 2.0 A cm−2, far exceeding commercial Pt/C after H2/10 ppm CO poisoning and H2/5 ppm H2S poisoning tests, respectively. Density functional theory (DFT) indicates that a coronal molecule layer with a steric confinement height (1.82 Å), constructed by DhmPy, emerges more intensive adsorption energy compared to 2,6-pyridinedicarboxamide (DcaPy) and 2,6-diacetylpyridine (DAcPy), thereby more effectively inhibits the adsorption of large-sized CO and H2S on Pt surface without affecting H2 traverse. This “work along both lines” mechanism with the resistance of both CO and H2S provides a new and promising design thought for high CO and sulfur tolerant PEMFC anodes.

Self‐assembly Promoted Crystallization of Diblock Copolypeptoids in Solution†

Comprehensive SummaryGreat efforts have been lately devoted to fabricating well‐defined nanostructures using crystallization‐driven self‐assembly (CDSA) strategy. The influence of self‐assembly on crystallization is also of great interest. Here, a series of amphiphilic diblock copolypeptoids poly(N‐allylglycine)‐b‐poly(N‐octylglycine) modified with cysteamine hydrochloride ((PNAG‐g‐NH2)‐b‐PNOG) were synthesized by ring‐opening polymerization (ROP) and post‐polymerization functionalization. The diblock copolypeptoid is comprised of one hydrophobic crystalline PNOG block and one hydrophilic amorphous block, which can aggregate into nanostructured assemblies with soluble PNAG‐g‐NH2 as the corona layer and PNOG as the inner core in aqueous solution. With a systematic study by differential scanning calorimetry (DSC) and wide‐angle X‐ray scattering (WAXS), we demonstrated that the self‐assembly of the block copolymers strengthens the crystallization of the PNOG block.

Effects of positive corona on upward leader initiation from tall building by 3D numerical simulation

The initiation of the stable upward leader (SUL) is an important criterion to judge whether a building can be struck by lightning. The corona layer above the tip of a building caused by thunderstorm will affect upward leader initiation; however, there are few studies on the degree of its specific impact. Therefore, based on the established three-dimensional corona discharge model (Guo et al., 2022) and the dynamic critical length criterion of initial streamer as reported by Guo et al. (2020), we establish an SUL initiation model with corona discharge at the tip of the tall building. It is found that the simulated results of our model (considering corona discharge) match well with actual observations. The model is then used to simulate buildings with different height and different peak current of lightning strike (IP). The effect of positive corona discharge at the tip of the building on the initiation of the positive SUL during downward negative cloud-to-ground flash is discussed. The results show the following: 1) for certain IP values, the effect of corona discharge at the tip of the building has a greater effect on taller buildings than shorter ones. 2) For buildings of the same height, as Ip decreases, the effect of corona discharge at the tip of the building becomes greater. For example, for an IP of 20 kA and an Hb of 200 m, at the moment of the SUL initiated from the building, the height of the DL tip above the ground is 550 m when the corona layer is considered in the simulation and is 861 m when which is not considered. The difference between them have reached at 36%.

Theoretical Analysis of External Insulation of Typical Electric Equipment under Impulse Voltage and Research on Design and Verification Method of Margin

Lightning impulse voltage, one of the typical characteristic working conditions for assessing high-voltage power equipment, can be divided into two forms, namely full wave, and chopped wave. The external structure size of the power equipment directly depends on the lightning impulse voltage, but how lightning impulse voltage relates to the external structure size of the power equipment needs to be carefully studied. Firstly, the theoretical analytical expressions of full wave and chopped wave lightning waveforms are given from the perspective of theoretical formulas. And the lightning waveform is considered to be a polynomial superposition of exponential functions. Based on this, the discussion is divided into two typical insulation structure scenarios: 1) the verification and analysis of the space net distance of a 10 m class super long composite insulator; 2) the analysis of the relationship between the breakdown electric field strength of 5 mm tiny oil gap and oil gap spacing. Further, the lightning impulse voltage test was conducted for large hardware structures, and the corona layer mathematical model was obtained through the precise observation of the structure with the ultraviolet imager. The research shows that the lightning impulse voltage mainly checks the external insulation performance of large insulation structures such as bushings and post-insulators. For the internal oil gap duct structure of the large converter transformer, the lightning impulse voltage mainly checks the micro gap insulation strength. Lightning impulse voltage also has a breakdown effect on SF6 insulation gas, but its internal gas decomposition mechanism needs theoretical and experimental analysis urgently. The research content of this paper has certain theoretical and practical guiding value for the optimization design of large insulation structures under lightning impulse voltage.

The Role of Water Hydrogen Bonds in the Formation of Associates and Condensates in Dispersions of Serum Albumin with Shungite Carbon and Quartz Nanoparticles

The role of the network of water hydrogen bonds in the regulation of the intermolecular interaction’s responsible for colloidal stability of dispersions has been studied in order to search for general patterns of interaction between water, nanoparticles, and bio-macromolecules. Raman spectroscopy for mixed dispersions of bovine serum albumin (SA), shungite carbon nanoparticles (ShC NPs), and quartz nanoparticles (quartz NPs) was performed within the wave number range 3200–3600 cm−1. The main spectral lines in this range are caused by the OH stretch vibrations of water molecules. We analyzed the state of the water hydrogen bonding network for dispersions of varied ratios of both fatty acid-containing and fatty acid-free SA macromolecules, ShC NPs, and silica NPs in the range 0.01–10 mg/mL.We used dynamic light scattering to control the sizes of the protein associates and protein associates with ShC NPs and quartz NPs. The strength of the hydrogen bonds in water depends essentially non-linearly, but in a qualitatively similar way, on the concentrations of the dispersion components. The initial strengthening of the bonds is followed by their loosening with a further increase in the concentration of the components. This is accompanied by the association of the dispersion components. We estimate the thickness of the protein corona layer as 20–25 nm for ShC NPs and 28–33 nm for quartz NPs, depending on the SA concentration. Colloidal stability of the aqueous dispersion is determined almost completely by an association of the protein with NPs. In contrast, colloidal stability of a pure protein solution is regulated by the formation of protein clusters of two main types and sizes. The association effects of SA with ShC NPs are evident in microscopic images of condensate films. The structures differ significantly for native and fatty acid-free SA in shape and size.

Probing the Protein Corona of Nanoparticles in a Fluid Flow by Single-Particle Differenced Resonance Light Scattering Correlation Spectroscopy.

The protein corona of nanoparticles (NPs) plays a crucial role in determining NPs' biological fates. Here, a novel measurement strategy was proposed to in situ investigate the protein corona formed in the NPs with the home-built dual-wavelength laser-irradiated differenced resonance light scattering correlation spectroscopy (D-RLSCS) technique, combined with the modified generation method of the D-RLSCS curve. With the measurement strategy, the dissociation constants and the binding rates between proteins and gold nanoparticles (GNPs) were determined based on the binding-induced ratiometric diffusion change of NPs (the ratio of characteristic rotational diffusion time to translational one), using the formation of the protein corona of bovine serum albumin (BSA) or fibrinogen (FIB) on gold nanoparticles as a model. It was found that BSA shows a stronger binding constant and faster binding rate to gold nanospheres (GNSs) compared with those of FIB. Meanwhile, the dynamic behavior of the protein corona in a fluid flow mimicking biological vessels was further studied based on the combination of the D-RLSCS technique with a microfluidic channel. The measurement results indicated that some "loose" protein corona layers would strip off the surface of NPs within the microchannel due to the fluid sheath force. This method can provide the comprehensive information of a protein corona by averaging the diffusion behavior of many particles different from some conventional methods and overcome the shortcomings of conventional correlation spectroscopy methods.

Hall instability driven seeding of helical magneto-Rayleigh–Taylor instabilities in axially premagnetized thin-foil liner Z-pinch implosions

Helical magneto-Rayleigh–Taylor instability (MRTI) structures have been observed in z-pinch-driven liner implosion experiments with a pre-imposed axial magnetic field. We show that the formation of these helical structures can be described by a Hall magnetohydrodynamical (HMHD) model. We used the 3D extended magnetohydrodynamics simulation code PERSEUS (which includes Hall physics) [Seyler and Martin, Phys. Plasmas 18, 012703 (2011)] to study these helical instabilities and show that a Hall interchange instability in low-density coronal plasma immediately surrounding the dense liner is responsible for producing helically oriented effects in the magnetic field and current density within the coronal layer. This seeds the helical pitch angle of the MRTI even when other proposed helical seeding mechanisms are either not present in the experiments or not accounted for in the simulations. For example, this mechanism does not require low-density power-feed plasmas to be swept in from large radius or the development of electrothermal instabilities. The Hall Instability is, thus, a new, independent explanation for the origin of the helical instabilities observed in axially premagnetized liner experiments. Simulation results supporting this mechanism are presented.

CXCL10-coronated thermosensitive “stealth” liposomes for sequential chemoimmunotherapy in melanoma

The interplay of liposome-protein corona hinders the clinical application of liposomes due to active macrophage sequestration and rapid plasma clearance. Here we showed that, CXCL10 as a therapeutic protein was coronated the thermosensitive liposomes to form stealth-like nanocarriers (CXCL10/TSLs). Decoration of the corona layer of CXCL10/TSLs by hyaluronic acid conjugated oridonin (ORD/CXCL10/TSLs), overcame the “fluid barrier” built by biological proteins, drastically reduced capture by leukocytes in whole blood, allowed the specific targeting of tumor sites. Multifunctional medicine ORD/CXCL10/TSLs with hyperthermia drove the sustained cytokine-CXCL10 inflammatory loop to switch macrophage phenotype to M1-like, expand tumor-infiltrating natural killer cells and induce intratumoral levels of interferon-γ. Oridonin synergized with CXCL10 during ORD/CXCL10/TSLs treatment, downregulated PI3K/AKT and Raf/MEK signaling for M1-like polarization and migration inhibition. Furthermore, ORD/CXCL10/TSLs potently synergized with anti-PD-L1 antibody in mice bearing metastatic melanoma, induced sustained immunological memory and controlled metastatic spread.

Understanding the extracellular vesicle surface for clinical molecular biology.

Extracellular vesicles (EVs) are lipid‐membrane enclosed nanoparticles that play significant roles in health and disease. EVs are abundant in body fluids and carry an array of molecules (proteins, lipids, nucleic acids and glycans) that reflect the identity and activity of their cell‐of‐origin. While the advent of high throughput omics technologies has allowed in‐depth characterisation of EV compositions, how these molecular species are spatially distributed within EV structures is not well appreciated. This is particularly true of the EV surface where a plethora of molecules are reported to be both integral and peripherally associated to the EV membrane. This coronal layer or ‘atmosphere’ that surrounds the EV membrane contributes to a large, highly interactive and dynamic surface area that is responsible for facilitating EV interactions with the extracellular environment. The EV coronal layer harbours surface molecules that reflect the identity of parent cells, which is likely a highly valuable property in the context of diagnostic liquid biopsies. In this review, we describe the current understanding of the mechanical, electrostatic and molecular properties of the EV surface that offer significant biomarker potential and contribute to a highly dynamic interactome.

Protein corona-driven nanovaccines improve antigen intracellular release and immunotherapy efficacy.

During vaccine delivery in vivo, the vaccine carrier dynamically adsorbs the surrounding proteins or biomacromolecules to form a protein corona layer, which determines the physiological and therapeutic responses of the vaccine. Although the importance of the protein corona effect in drug delivery is widely accepted, understanding of the rational use of the protein corona to improve antigen controlled release is still sparse. Here, we constructed a protein corona-driven nanovaccine (PCNV), which has the dual effects of resisting the protein corona-induced antigen extracellular release and promoting protein corona-triggered antigen cytosolic release under reductive conditions. Specifically, the nanovaccine was formulated via the assembly of fluorinated dendrigraft-poly-lysine and cleavable antigen-CpG conjugate. Before entering antigen-presenting cells (APCs), the anchoring effect of CpG was used to avoid the dissociation of antigens from the carrier even under the protein corona effect. While nanovaccine enters the APCs, the intracellular reducing conditions can induce a break in the disulfide bond between CpG and antigen. Notably, at the same time, the intracellular protein corona effect triggers antigen release from the carrier and achieves efficient antigen presentation. In addition, the PCNV produced a significant prophylactic and therapeutic antitumor response in the mouse model. Therefore, the rational use of the protein corona effect provides an effective strategy for vaccine delivery.

Antibacterial Effect of Silver Nanoparticles Is Stronger If the Production Host and the Targeted Pathogen Are Closely Related.

Microbial resistance to antibiotics is one of the key challenges that lead to the search for alternate antimicrobial treatment approaches. Silver nanoparticles (AgNPs) are well known for their antimicrobial effects against a wide variety of drug-resistant microorganisms. AgNPs can be synthesized using microbial hosts, using a green and economical synthesis route, which produces extremely stable and highly active nanoparticles. Such green AgNPs are coated with a biological coating often referred to as a corona, originating from the production microorganism. In this study, we asked whether the composition of the biological corona might influence the antimicrobial activity of green AgNPs. To investigate this, we produced AgNPs in Pseudomonas putida KT2440 and Escherichia coli K12 MG1655, and tested them against pathogen species from the corresponding genera. AgNPs exhibited a size range of 15–40 nm for P. putida and 30–70 nm for E. coli, and both types of nanoparticles were surrounded by a thick biological corona layer, providing extreme stability. The nanoparticles remained stable over long periods and exhibited negative zeta potential values. P-AgNPs (obtained from P. putida) were tested against pathogenic Pseudomonas aeruginosa PAO1, and E-AgNPs (obtained from E. coli) were tested against pathogenic Escherichia coli UTI 89. Antimicrobial studies were conducted by Minimum bactericidal concentration (MBC), live/dead staining and SEM analysis. MBC of P-AgNPs against P. aeruginosa was 1 μg/mL, and MBC of E-AgNPs against E. coli UTI 89 was 8 μg/mL. In both cases, the MBC values were superior to those of green AgNPs produced in organisms unrelated to the target pathogens, available in the literature. Our results suggest that NPs produced in microorganisms closely related to the target pathogen may be more effective, indicating that the composition of the biological corona may play a crucial role in the antimicrobial mechanism of AgNPs.