Self-assembled Nanoparticles Research Articles

Nanoparticle display of neuraminidase elicits enhanced antibody responses and protection against influenza A virus challenge

Current Influenza virus vaccines primarily induce antibody responses against variable epitopes in hemagglutinin (HA), necessitating frequent updates. However, antibodies against neuraminidase (NA) can also confer protection against influenza, making NA an attractive target for the development of novel vaccines. In this study, we aimed to enhance the immunogenicity of recombinant NA antigens by presenting them multivalently on a nanoparticle carrier. Soluble tetrameric NA antigens of the N1 and N2 subtypes, confirmed to be correctly folded by cryo-electron microscopy structural analysis, were conjugated to Mi3 self-assembling protein nanoparticles using the SpyTag-SpyCatcher system. Immunization of mice with NA-Mi3 nanoparticles induced higher titers of NA-binding and -inhibiting antibodies and improved protection against a lethal challenge compared to unconjugated NA. Additionally, we explored the co-presentation of N1 and N2 antigens on the same Mi3 particles to create a mosaic vaccine candidate. These mosaic nanoparticles elicited antibody titers that were similar or superior to the homotypic nanoparticles and effectively protected against H1N1 and H3N2 challenge viruses. The NA-Mi3 nanoparticles represent a promising vaccine candidate that could complement HA-directed approaches for enhanced potency and broadened protection against influenza A virus.

Self-assembled Au-CQDs nanofluids with excellent solar absorption and medium–high temperature stability for solar energy harvesting

Nanofluids-based direct absorption solar collectors are promising candidates for medium–high-temperature solar energy harvesting. However, nanofluids’ complicated preparation process and undesirable high-temperature stability have hindered their practical applications. Herein, we propose a facile method for synthesizing gold/carbon quantum dots (Au-CQDs) nanofluids by directly carbonizing the base fluid and spontaneously assembling with Au nanoparticles (AuNPs) triggered by high temperatures. The results indicate that the self-assembled Au-CQDs nanofluids can maintain high stability at 110 °C for 100 h without precipitation and keep excellent photothermal conversion performance under 10 sun irradiation. The concentration and particle size of AuNPs are crucial factors affecting the self-assembly process. By modulating the microscopic morphologies of the self-assembled nanoparticles, the extinction coefficient of the prepared nanofluids is up to 88.7 % at a low loading of 30 ppm. The nanofluids can reach an equilibrium temperature of 50 °C under 1 sun irradiation, 10.4 °C higher than the base fluid due to the enhanced plasmonic effects and stability resulting from the CQDs dotted AuNPs. This work offers a new strategy to fabricate highly stable nanofluids with excellent light absorption properties for efficient solar thermal applications.

Use of Transient Transfection for cGMP Manufacturing of eOD-GT8 60mer, a Self-Assembling Nanoparticle Germline-Targeting HIV-1 Vaccine Candidate.

We describe the current Good Manufacturing Practice (cGMP) production and subsequent characterization of eOD-GT8 60mer, a glycosylated self-assembling nanoparticle HIV-1 vaccine candidate and germline targeting priming immunogen. Production was carried out via transient expression in the human embryonic kidney 293 (HEK293) cell line followed by a combination of purification techniques. A large-scale cGMP (200 L) production run yielded 354 mg of the purified eOD-GT8 60mer drug product material, which was formulated at 1 mg/mL in 10% sucrose in phosphate-buffered saline (PBS) at pH 7.2. The clinical trial material was comprehensively characterized for purity, antigenicity, glycan composition, amino acid sequence, and aggregation and by several safety-related tests during cGMP lot release. A comparison of the purified products produced at the 1 L scale and 200 L cGMP scale demonstrated the consistency and robustness of the transient transfection upstream process and the downstream purification strategies. The cGMP clinical trial material was tested in a Phase 1 clinical trial (NCT03547245), is currently being stored at -80 °C, and is on a stability testing program as per regulatory guidelines. The methods described here illustrate the utility of transient transfection for cGMP production of complex products such as glycosylated self-assembling nanoparticles.

Mechanistic understanding of nanoparticle interactions to achieve highly-ordered arrays through self-assembly for sensitive surface-enhanced Raman scattering detection of trace thiram

Over the last few decades, there is increasing worldwide concern over human health risks associated with extensive use of pesticides in agriculture. Developing excellent SERS substrate materials to achieve highly sensitive detection of pesticide residues in the food is very necessary owing to their serious threat to human health through food chains. Self-assembled metallic nanoparticles have been demonstrated to be excellent SERS substrate materials. Hence, alkanethiols-protected gold nanoparticles have been successfully prepared for forming larger-scale two-dimensional monolayer films. These films can be disassembled into a fluid state and re-assembled back to crystallized structure by controlling surface pressure. Further investigations reveal that their self-assembled structures are mainly dependent on the diameter of gold nanoparticles and ligand length. These results suggest that the size ratio of nanoparticle diameter/ligand length within the range of 4.45–2.35 facilitates the formation of highly ordered 2D arrays. Furthermore, these arrays present excellent Surface-Enhanced Raman Scattering performances in the detection of trace thiram, which can cause environmental toxicity to the soil, water, animals and result in severe damage to human health. Therefore, the current study provides an effective way for preparing monodispersed hydrophobic gold nanoparticles and forming highly ordered 2D close-packed SERS substrate materials via self-assembly to detect pesticide residues in food. We believe that, our research provides not only advanced SERS substrate materials for excellent detection performance of thiram in food, but also novel fundamental understandings of self-assembly, manipulation of nanoparticle interactions, and controllable synthesis.

High-efficiency green light emission from InGaN/GaN using localized surface plasmon resonance tuned by combination of Ag nanoparticles and dielectric thin film

We achieved significant enhancements in green light emission (550 nm) from InGaN/GaN quantum wells (QWs) by tuning the localized surface plasmon resonance (LSPR) of self-assembled Ag nanoparticles (NPs) through the application of a SiO2 thin film. The LSPR wavelength of Ag NPs was shifted towards shorter wavelengths by 80 nm using a 5 nm SiO2 layer to separate Ag NPs from GaN surface, thereby aligning it effectively with the green region. This strategic placement of Ag NPs and a 5 nm SiO2 film resulted in significant enhancements of photoluminescence (PL) by 15- and 8.8-fold with 5 and 11 nm GaN cap layers, respectively. The LSPR of Ag NPs on a SiO2 thin film facilitated a longer possible distance for the coupling between surface plasmons (SPs) and excitons in a QW. Traditionally, the distance between SPs-generating metal and a QW has been maintained at 10 nm to achieve substantial enhancements. Remarkably, even with a 25 nm cap layer, Ag NPs on a 5 nm SiO2 film boosted PL by 3.1-fold. The enhancements attributable to Ag NPs on SiO2 films were superior, reaching up to 4.8 times greater than those of Ag NPs on GaN surfaces. Additionally, the PL enhancement factors calculated using the finite differential time domain (FDTD) method aligned closely with experimental results.

Self-Assembling P38 Peptide Inhibitor Nanoparticles Ameliorate the Transition from Acute to Chronic Kidney Disease by Suppressing Ferroptosis.

Accumulating evidence highlights p38 as a crucial factor highly activated during the process of acute kidney injury (AKI), but the application of p38 inhibitor in AKI is quite limited due to the low efficiency and poor kidney-targeting ability. Herein, a novel self-assembling peptide nanoparticle with specific p38-inhibiting activity is constructed, which linked mitogen-activated protein kinase kinase 3b (MKK3b), the functional domain of p38, with the cell-penetrating TAT sequence, ultimately self-assembling into TAT-MKK3b nanoparticles (TMNPs) through tyrosinase oxidation. Subsequent in vitro and in vivo studies demonstrated that TMNPs preferably accumulated in the renal tubular epithelial cells (RTECs) through forming protein coronas by binding to albumin, and strongly improved the reduced renal function of ischemia-reperfusion injury (IRI)-induced AKI and its transition to chronic kidney disease (CKD). Mechanically, TMNPs inhibited ferroptosis via its solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) axis-inducing capacity and synergistic potent antioxidant property in AKI. The findings indicated that the multifunctional TMNPs exhibited renal targeting, ROS-scavenging, and ferroptosis-mitigating capabilities, which may serve as a promising therapeutic agent for the treatment of AKI and its progression to CKD.

Efficient nanopatterning of Ge surface induced by oblique argon cluster ion beam

The evolution of the self-assembled nanostructures formed on the Ge (100) surface as a result of sputtering by an obliquely incident argon cluster ion beam is studied. The bombardment was carried out with Ar1000+ ions at energy of 10 keV and angle of incidence of 60˚ from the normal while varying the ion fluence from 8 × 1014 up to 2 × 1016 ions/cm2. It is found that parallel-mode ordered ripples with significant aspect ratios can be produced on the Ge surface at a minimum sputtering depth. Such nanostructures have not previously been formed on the Ge surface with conventional argon ions. Our findings prove that argon cluster ion beam is effective for nanopatterning the surface of single-component semiconductors.

A ferritin nanoparticle vaccine based on the hemagglutinin extracellular domain of swine influenza A (H1N1) virus elicits protective immune responses in mice and pigs.

Swine influenza viruses (SIVs) pose significant economic losses to the pig industry and are a burden on global public health systems. The increasing complexity of the distribution and evolution of different serotypes of influenza strains in swine herds escalates the potential for the emergence of novel pandemic viruses, so it is essential to develop new vaccines based on swine influenza. Here, we constructed a self-assembling ferritin nanoparticle vaccine based on the hemagglutinin (HA) extracellular domain of swine influenza A (H1N1) virus using insect baculovirus expression vector system (IBEVS), and after two immunizations, the immunogenicities and protective efficacies of the HA-Ferritin nanoparticle vaccine against the swine influenza virus H1N1 strain in mice and piglets were evaluated. Our results demonstrated that HA-Ferritin nanoparticle vaccine induced more efficient immunity than traditional swine influenza vaccines. Vaccination with the HA-Ferritin nanoparticle vaccine elicited robust hemagglutinin inhibition titers and antigen-specific IgG antibodies and increased cytokine levels in serum. MF59 adjuvant can significantly promote the humoral immunity of HA-Ferritin nanoparticle vaccine. Furthermore, challenge tests showed that HA-Ferritin nanoparticle vaccine conferred full protection against lethal challenge with H1N1 virus and significantly decreased the severity of virus-associated lung lesions after challenge in both BALB/c mice and piglets. Taken together, these results indicate that the hemagglutinin extracellular-based ferritin nanoparticle vaccine may be a promising vaccine candidate against SIVs infection.

Interfacially self-assembled Fe2O3 nanoparticles decorated kaolinite for high performance anti-bacterial and anti-cancerous agents

Nano-engineering of naturally occurring layered materials incorporates enhanced inherent properties for bionanotechnology. Here, kaolinite was treated with a concentrated aqueous ferrous sulfate solution at 100 °C for 1 h for surface modification. Therefore, interfacially self-assembled nanostructure of ferric oxide (Fe2O3) decorated kaolinite composites (FDKC) was fabricated from cationically (Fe2+) modified kaolinite (CMK) after calcinations at 680 °C. Characterized nanocomposites by ATR-IR, EDS, XRD and SEM were tested for antimicrobial activity and antibiofilm activity against Gram negative bacteria Escherichia coli (E. coli), Klebsiella spp (K. spp) and Salmonella typhi (S typhi), as well as Gram positive Staphylococcus aureus, while cytotoxic activity was observed against HeLa cell. CMK and FDKC showed significantly higher antimicrobial activity and biofilm destruction ability than virgin kaolinite (p < 0.05). Besides, FDKC showed the highest anticancer activity in HeLa cell at moderate concentration. The synergistic effect of nanocomposites would offer the modulation of enhanced electronic and physical properties from a simple technology to improve inherent antimicrobial activity and cell toxicity of kaolinite for targeted assay.

Induced Huge Optical Activity in Nanoplatelet Superlattice.

Chiral superstructures with unique chiroptical properties that are not inherent in the individual units are essential in applications such as 3D displays, spintronic devices, biomedical sensors, and beyond. Generally, chiral superstructures are obtained by tedious procedures exploring various physical and chemical forces to break spatial symmetry during the self-assembly of discrete nanoparticles. In contrast, we herein present a simple and efficient approach to chiral superstructures by intercalating small chiral molecules into preformed achiral superstructures. As a model system, the chiral CdSe nanoplatelet (NPL) superlattice exhibits a giant and tunable optical activity with the highest g-factor reaching 3.09 × 10-2 to the excitonic transition of the NPL superlattice, nearly 2 orders of magnitude higher than that of the corresponding separated chiral NPLs. The theoretical analysis reveals that the chiral deformation in the NPL superlattice induced by the chiral perturbation of the small chiral molecules is critical to the observed huge optical activity. We anticipate that this research lays a foundation for understanding and applying chiral inorganic nanosystems.

A Self-Assembling Pfs230D1-Ferritin Nanoparticle Vaccine Has Potent and Durable Malaria Transmission-Reducing Activity.

Malaria is caused by eukaryotic protozoan parasites of the genus Plasmodium. There are 249 million new cases and 608,000 deaths annually, and new interventions are desperately needed. Malaria vaccines can be divided into three categories: liver stage, blood stage, or transmission-blocking vaccines. Transmission-blocking vaccines prevent the transmission of disease by the mosquito vector from one human to another. Pfs230 is one of the leading transmission-blocking vaccine antigens for malaria. Here, we describe the development of a 24-copy self-assembling nanoparticle vaccine comprising domain 1 of Pfs230 genetically fused to H. pylori ferritin. The single-component Pfs230D1-ferritin construct forms a stable and homogenous 24-copy nanoparticle with good production yields. The nanoparticle is highly immunogenic, as two low-dose vaccinations of New Zealand White rabbits elicited a potent and durable antibody response with high transmission-reducing activity when formulated in two distinct adjuvants suitable for translation to human use. This single-component 24-copy Pfs230D1-ferritin nanoparticle vaccine has the potential to improve production pipelines and the cost of manufacturing a potent and durable transmission-blocking vaccine for malaria control.

Effect of Block Copolymer Self-Assembly on Phase Separation in Photopolymerizable Epoxy Blends.

Directing self-assembly of photopolymerizable systems is advantageous for controlling polymer nanostructure and material properties, but developing techniques for inducing ordered structure remains challenging. In this work, well-defined diblock or random copolymers were incorporated into cationic photopolymerizable epoxy systems to investigate the impact of copolymer architecture on self-assembly and phase separated nanostructures. Copolymers consisting of poly(hydroxyethyl acrylate)-x-(butyl acrylate) were prepared using photoiniferter polymerization to control functional group placement and molecular weight/polydispersity. Prepolymer configuration and concentration induced distinctly different effects on the resin flow and photopolymerization kinetics. The diblock copolymer self-assembled into nanostructured phases within the resin matrix, whereas the random copolymer formed an isotropic mixture. Rapid photopolymerization and ambient temperature conditions during cure facilitated retention of the self-assembled phases, leading to considerably different composite morphology and thermomechanical behavior. Increased loading of the diblock copolymer induced long-range ordered cocontinuous structures. Even with nearly identical prepolymer composition, controlled nanophase separation resulted in significantly enhanced tensile properties relative to those of the isotropic system. This work demonstrates that controlling phase separation with a block copolymer architecture allows access to nanostructured photopolymers with unique and enhanced properties.

Solubilization mechanism of α-glycosylated naringin based on self-assembled nanostructures and its application to skin formulation

We previously reported that α-glycosylated naringin (naringin-G), synthesized by enzyme-catalyzed transglycosylation, can enhance the solubility of poorly water-soluble compounds without surface-active property. However, the solubilization mechanism has not been fully elucidated. In this study, the solubilization mechanism of naringin-G was investigated using nuclear magnetic resonance (NMR) spectroscopy, and its application in skin formulations was further investigated. 1H NMR and dynamic light scattering measurements at various concentrations confirmed the self-assembled nanostructures of naringin-G above a critical aggregation concentration of approximately 2.2 mg/mL. Two-dimensional 1H–1H nuclear Overhauser effect spectroscopy and solubility tests revealed that flavone with poor water solubility, could be solubilized in its self-assembled structure with a stoichiometric relationship with naringin-G. When naringin-G was included in the skin formulation, the permeated amount and permeability coefficient (Papp) of flavones improved up to four times with increasing amounts of naringin-G. However, flavone solubilization by adding an excessive amount of naringin-G resulted in a decreased permeated amount and Papp of flavones, indicating the interplay between the apparent solubility and skin permeability of flavones. Naringin-G, which forms a nanoaggregate structure without exhibiting surface-active properties, has the potential to enhance the solubility and skin permeation of poorly water-soluble compounds.

Self-Assembled Nanoparticles from the Amphiphilic Prodrug of Resiquimod for Improved Cancer Immunotherapy.

Tumor-associated macrophages (TAMs) usually adopt a tumor-promoting M2-like phenotype, which largely impedes the immune response and therapeutic efficacy of solid tumors. Repolarizing TAMs from M2 to the antitumor M1 phenotype is crucial for reshaping the tumor immunosuppressive microenvironment (TIME). Herein, we developed self-assembled nanoparticles from the polymeric prodrug of resiquimod (R848) to reprogram the TIME for robust cancer immunotherapy. The polymeric prodrug was constructed by conjugating the R848 derivative to terminal amino groups of the linear dendritic polymer composed of linear poly(ethylene glycol) and lysine dendrimer. The amphiphilic prodrug self-assembled into nanoparticles (PLRS) of around 35 nm with a spherical morphology. PLRS nanoparticles could be internalized by antigen-presenting cells (APCs) in vitro and thus efficiently repolarized macrophages from M2 to M1 and facilitated the maturation of APCs. In addition, PLRS significantly inhibited tumor growth in the 4T1 orthotopic breast cancer model with much lower systemic side effects. Mechanistic studies suggested that PLRS significantly stimulated the TIME by repolarizing TAMs into the M1 phenotype and increased the infiltration of cytotoxic T cells into the tumor. This study provides an effective polymeric prodrug-based strategy to improve the therapeutic efficacy of R848 in cancer immunotherapy.

In-situ self-assembly growth of controllable gold nanoparticles film

Because of the strong light absorption and/or scattering, nano scaled gold has many favorable optic and electric properties. With the continuous miniaturization of nano photoelectronic devices and nano electromechanical systems, there is an urgent demand for controllable and tailored gold nanoparticles film with excellent performance. Here, a modified HAuCl4-NaOH-CTAB (cetyltrimethylammonium bromide) aqueous solution system was utilized to self-assembly synthesize gold nanofilm on glass substrates. The high concentration NaOH is not only reducing Au3+ to Au0, but facilitating interfacial assembly of gold nanostructure at liquid–solid interface via etching glass surface. Based on this growth kinetic, the gradient, well-designed and in-situ growing gold nanoparticles film can be achieved on any SiO2 contained substrates by controlling the growth time in the reaction system. Furthermore, the in-situ self-assembled gold nanoparticles film can be act as plasmon substrates for surface-enhanced Raman scattering (SERS) or plasmonic enhanced semiconductor lasing, even gold electrodes.

MRNA-LNP prime boost evolves precursors toward VRC01-like broadly neutralizing antibodies in preclinical humanized mouse models.

Germline-targeting (GT) protein immunogens to induce VRC01-class broadly neutralizing antibodies (bnAbs) to the CD4-binding site of the HIV envelope (Env) have shown promise in clinical trials. Here, we preclinically validated a lipid nanoparticle-encapsulated nucleoside mRNA (mRNA-LNP) encoding eOD-GT8 60mer as a soluble self-assembling nanoparticle in mouse models. In a model with three humanized B cell lineages bearing distinct VRC01-precursor B cell receptors (BCRs) with similar affinities for eOD-GT8, all lineages could be simultaneously primed and undergo diversification and affinity maturation without exclusionary competition. Boosts drove precursor B cell participation in germinal centers; the accumulation of somatic hypermutations, including in key VRC01-class positions; and affinity maturation to boost and native-like antigens in two of the three precursor lineages. We have preclinically validated a prime-boost regimen of soluble self-assembling nanoparticles encoded by mRNA-LNP, demonstrating that multiple lineages can be primed, boosted, and diversified along the bnAb pathway.

Highly Ordered Nanoassemblies of Janus Spherocylindrical Nanoparticles Adhering to Lipid Vesicles.

In recent years, there has been a heightened interest in the self-assembly of nanoparticles (NPs) that is mediated by their adsorption onto lipid membranes. The interplay between the adhesive energy of NPs on a lipid membrane and the membrane's curvature energy causes it to wrap around the NPs. This results in an interesting membrane curvature-mediated interaction, which can lead to the self-assembly of NPs on lipid membranes. Recent studies have demonstrated that Janus spherical NPs, which adhere to lipid vesicles, can self-assemble into well-ordered nanoclusters with various geometries, including a few Platonic solids. The present study explores the additional effect of geometric anisotropy on the self-assembly of Janus NPs on lipid vesicles. Specifically, the current study utilized extensive molecular dynamics simulations to investigate the arrangement of Janus spherocylindrical NPs on lipid vesicles. We found that the additional geometric anisotropy significantly expands the range of NPs' self-assemblies on lipid vesicles. The specific geometries of the resulting nanoclusters depend on several factors, including the number of Janus spherocylindrical NPs adhering to the vesicle and their aspect ratio. The lipid membrane-mediated self-assembly of NPs, demonstrated by this work, provides an alternative cost-effective route for fabricating highly engineered nanoclusters in three dimensions. Such structures, with the current wide range of material choices, have great potential for advanced applications, including biosensing, bioimaging, drug delivery, nanomechanics, and nanophotonics.

Highly Porous ZnO/CNT Hybrid Microclusters for Superior UV Photodetection.

The formation of nanoscale junctions among nanoparticles in self-assembled nanostructures is crucial for improving both interfacial conductivity and structural integrity. However, the inherent reliance on weak van der Waals forces to hold nanoparticles together poses challenges in developing commercially viable devices due to their inefficient carrier transport characteristics. This study presents the successful integration of carbon nanotubes (CNTs) into highly porous nanomicrocluster arrays of ZnO, resulting in the formation of cohesive and crack-free highly porous ZnO/CNT heterojunction films. This integration marks a significant improvement in UV photodetection performance, demonstrating a record-high photocurrent to dark current ratio of 3.3 × 106 and an exceptional responsivity of 18.5 A/W at a low bias of 0.5 V and under an ultra low light density of 25 μW/cm2. These findings underscore the efficacy of this high-performance structure as a versatile and scalable platform technology for the rapid, cost-effective fabrication of hybrid photodetectors in wearable and portable devices.

Magnetic zinc oxide/silica microbeads for the photocatalytic degradation of azo dyes

Photocatalysis is a promising technique for the complete degradation of azo dyes that are present in wastewater. In this work, a new photocatalyst in the form of ZnO/Fe3O4/SiO2 hybrid microbeads was fabricated for the photocatalytic degradation of methylene blue. The microbeads were synthesised through self-assembly and subsequent agglomeration of nanoparticles within an aqueous phase of a water-in-oil emulsion template. Photocatalytic degradation experiments were conducted through exposure of a methylene blue solution to UV light. The hybrid microbeads performed better than ZnO powder at the same initial dye and ZnO concentration because of higher adsorption and degradation. The initial concentration of dye solution and catalyst dosage have a significant impact on the degradation. Higher degradation is seen with lower initial dye concentration and higher catalyst dosage. The presence of magnetic nanoparticles within the beads allows for their full recovery and reuse for degradation experiments. Complete degradation of dye was achieved using the new ZnO/Fe3O4/SiO2 microbeads.

Biomaterials for Targeting Endoplasmic Reticulum in Cancer.

Endoplasmic reticulum (ER) is one of the most important sub-cellular organelles which controls myriads of biological functions including protein biosynthesis with proper functional folded form, protein misfolding, protein transport into Golgi body for secretion, Ca2+ homeostasis and so on. Subsequently, dysregulation in ER function leads to ER stress followed by disease pathology like cancer. Hence, targeting ER in the cancer cells emerged as one of the futuristic strategies for cancer treatment. However, the major challenge is to selectively and specifically target ER in the sub-cellular milieu in the cancer tissues, due to the lack of ER targeting chemical moieties to recognize the ER markers. To address this, in the last decade, numerous biomaterials were explored to selectively impair and image ER in cancer cells to induce ER stress. This review outlines those biomaterials which consists of carbon and silicon materials, lipid nanoparticles (liposomes and micelles), supramolecular self-assembled nanostructures, cell membrane-coated nanoparticles and metallic nanoparticles. Moreover, we also discuss the challenges and possible solutions of this promising field to usher the readers towards next-generation ER targeted cancer therapy.