Self-assembled Nanoparticles Research Articles

Self-Assembled Ce6-Peptide Nanoparticles Enhance NO Production and Photodynamic Therapy against Bacterial Infections

Self-Assembled Ce6-Peptide Nanoparticles Enhance NO Production and Photodynamic Therapy against Bacterial Infections

Review of: "Molecular Nanoelectronics and Simulation of Self-assembly (Nanoparticles)"

Review of: "Molecular Nanoelectronics and Simulation of Self-assembly (Nanoparticles)"

Role of polymer graft stiffness in electrostatic-driven self-assembly of nanoparticles in solutions.

Self-assembly of nanoparticles (NPs) in solution has garnered tremendous attention among researchers because of their electrical, chemical, and optoelectronic properties at the macroscale with potential applications in bio-imaging, bio-medicine, and therapeutics. Control of size, shape, and composition at the nanoscale is important in tuning the material's bulk properties. The grafting of NPs with polymers enables us to tune such bulk material properties at the nano level by controlling their assemblies, especially in solutions. The stiffness of grafts plays a crucial role in tuning the self-assembly of spherical NPs grafted with polyions (PGNs). Many recent studies based on single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) showed the potential applications of such assemblies. In this work, we have performed coarse-grained molecular dynamics (MD) simulations to understand the charge-driven self-assembly of PGNs by varying stiffness of polymer grafts, the grafting density, and graft length. Self-assembly of these PGNs leads to the formation of different structures driven by the rigidity of polyion chains and the electrostatic interactions. A dramatic change in morphological transitions can be achieved, ranging from rings, strings, and percolated structures and ordered to disordered aggregates by tuning the control parameters. The percolated structures form disordered structures upon annealing with potential applications in thermal under filling, neuromorphic devices, and biological systems including drug delivery, and therapeutics.

Excited-State Carrier Dynamics in Semiconducting Heterostructures from Self-Sorted NIR Active Dyes.

Heterostructures comprise two or more different semiconducting materials stacked either as co-assemblies or self-sorted based on their dynamics of aggregates. However, self-sorting in heterostructures is rather significant in improving the short exciton diffusion length and charge separation. Despite small organic molecules being known for their self-sorting nature, macrocyclic are hitherto unknown owing to unrestrained assemblies from extended π-conjugated systems. Herein, two near infrared region (NIR) active molecules comprised of porphyrin appended D-π-D (1) and A-π-A (2) have been reported to show the self-assembled 0D and 2D nanostructures via J-aggregates. Interestingly, the mixture of 1 and 2 reveals self-sorting at the molecular level promoting nanosphere and sheet structures which further rolled over to spheres through π-π stacking leading to core-shell type heterostructure. Consequently, electrical conductivity is 10 times higher than the individual assemblies due to excited state electron transfer from 1 to 2 in a mixture, confirmed by femto second-transient absorption spectroscopy and electrochemical impedance spectroscopy. These results suggest that controlling the self-sorted heterostructures fosters refining the electronic properties which pave the way for designing novel NIR-absorbed molecules for organic solar cells (OSCs).

Well-Defined PtCo@Pt Core-Shell Nanodendrite Electrocatalyst for Highly Durable Oxygen Reduction Reaction.

The rational design of efficient electrocatalysts with controllable structure and composition is crucial for enhancing the lifetime and cost-effectiveness of oxygen reduction reaction (ORR). PtCo nanocrystals have gained attention due to their exceptional activity, yet suffer from stability issues in acidic media. Herein, an active and highly stable electrocatalyst is developed, namely 3D Pt7Co3@Pt core-shell nanodendrites (NDs), which are formed through the self-assembly of small Pt nanoparticles (≈6nm). This unique structure significantly improves the ORR with an enhanced mass activity (MA) of 0.54 A mgPt -1, surpassing that of the commercial Pt/C (com-Pt/C) catalyst by three fold (0.17 A mgPt -1). The well-organized dendritic morphology, along with the Pt-rich shell, contributes significantly to the observed high catalytic activity and superior stability for acidic ORR, which exhibit a loss of 2.1% in MA and, impressively, an increase of 12.0% in specific activity (SA) after an accelerated durability test (ADT) of 40,000 potential-scanning cycles. This work offers insights for improving the design of highly stable Pt-based electrocatalysts for acidic ORR.

Dual Influence of Size and Electric Field on Gold Nanoparticles: Insights into 2D Monolayer Assembly.

Self-assembled gold nanoparticles (Au-NPs) possess distinctive properties that are highly desirable in diverse nanotechnological applications. This study meticulously explores the size-dependent behavior of Au-NPs under an electric field, specifically focusing on sizes ranging from 5 to 40 nm, and their subsequent assembly into 2D monolayers on an n-type silicon substrate. The primary objective is to refine the assembly process and augment the functional characteristics of the resultant nanostructures. Utilizing a multifaceted analytical approach encompassing X-ray diffraction (XRD) and scanning electron microscopy (SEM) with energy-dispersive X-ray spectroscopy (EDXS), atomic force microscopy (AFM), and COMSOL multiphysics simulation, this work yields comprehensive insights. Results reveal that the electric field and nanoparticle size critically influence assembly dynamics due to variations in surface energy and electrostatic interactions. Larger Au-NPs (20, 30, and 40 nm) experience enhanced dipolar interactions and more substantial polarizability, enabling more efficient alignment and organization under an applied electric field. This leads to the formation of structured, uniform monolayers with minimal vacancies and smoother surfaces. In contrast, smaller Au-NPs (5, 10, and 15 nm) exhibit lower polarizability, which hampers alignment and promotes clustering and voids. XRD analysis delineates notable disparities in peak intensities and positions: smaller Au-NPs exhibit diminished (111) peak intensities, indicative of uneven distribution and crystallinity, whereas larger particles manifest higher intensities and well-defined peaks across multiple crystallographic planes. SEM images portray diverse surface coverages with AFM corroborating that larger Au-NPs achieve uniform and continuous monolayers with minimal height variations. COMSOL simulations substantiate these findings by illustrating the efficient alignment and settling of larger Au-NPs under the electric field. This study bridges critical gaps in understanding how nanoparticle size modulates assembly dynamics and the resultant properties of 2D Au-NP monolayers, offering pivotal insights into engineering advanced nanostructured materials tailored to specific applications in electronics, coatings, photonics, and catalysis.

Enhanced chloramphenicol biodegradation and sustainable electricity generation via co-cultured electroactive biofilms modified with in-situ self-assembled gold nanoparticles and reduced graphene oxide.

Bioelectrochemical technology emerges as a promising approach for addressing the challenge of antibiotic residue contamination. This research innovated by incorporating in-situ self-assembled gold nanoparticles (Au-NPs) and reduced graphene oxide (rGO) into a co-cultured electroactive biofilm (EAB) of Raoultella sp. DB-1 and Shewanella oneidensis MR-1 (Au-rGO@R/S-C). Supported by the rGO scaffold, the embedding of Au-NPs at key intercellular sites, and the adhesion of extracellular polymeric substance (EPS), the Au-rGO@R/S-C EAB enhanced the bioelectrochemical performance of the inoculated microbial fuel cell (MFC), with a 34.4% increase in the maximum voltage output and a 1.95-fold rise in the maximum power density, enabling the complete degradation of 100mg/L chloramphenicol within 24h. Notably, the Au-rGO@R/S-C EAB adapted to increased chloramphenicol stress by amplifying EPS secretion, especially with an elevated protein/polysaccharide ratio. Further analysis indicated a positive correlation between excessive production of EPS, particularly the increase in tightly bound EPS, and the stability in balancing the self-protection and extracellular electron transfer efficiency of the Au-rGO@R/S-C EAB under environmental stress. Our findings present a crucial strategy for the rational engineering of EABs, leveraging their dual potential in both environmental remediation and clean energy production.

Tuning mucoadhesion and mucopenetration in self-assembled poly(lactic acid)-block-poly(oligoethylene glycol methacrylate) block copolymer nanoparticles by controlling side-chain lengths.

The capacity to tune the degree of mucoadhesion and mucopenetration of nanoparticles is essential to improving drug bioavailability, transport, and efficacy at mucosal interfaces. Herein, self-assembled nanoparticles (NPs) fabricated from amphiphilic block copolymers of poly(lactic acid) (PLA) and poly(oligo(ethylene glycol) methacrylate) (POEGMA) with various side chain lengths (PLA-POEGMAn) are reported to facilitate tunable mucosal interactions. PLA-POEGMAn nanoparticles with long PEG side chain lengths (n = 20, or 40) demonstrated mucoadhesive properties based on rheological synergism, calorimetric tracking of mucin-nanoparticle interactions, and the formation of larger NP-mucin hybrid structures; in contrast, NPs fabricated from block copolymers with shorter PEG side chains (n = 2/8-9 or n = 8,9) showed poor mucoadhesion but penetrated through the mucin layer with significantly higher permeation rates (>80%). All NP formulations showed good cytocompatibility (viability > 70%) with human corneal epithelial cells in vitro and no detectable acute in vivo ocular irritation in Sprague-Dawley rats. Coupled with the capacity of the synthetic route to easily incorporate different brush lengths and/or different functional groups into the hydrophilic block, we anticipate this approach may offer a solution in applications in which balancing mucoadhesion and mucopenetration is critical for enabling effective drug delivery.

Two-stage photodegradation of indomethacin molecular nanocomposites under extreme confinement.

The incorporation of a glassy material into a self-assembled nanoparticle (NP) film can produce highly loaded nanocomposites. Reduction of the NP diameter can lead to extreme nanoconfinement of the glass, significantly affecting the thermal and physical properties of the nanocomposite material. Here, we investigate the photostability and photodegradation mechanisms of molecular nanocomposite films (MNCFs) produced from the infiltration of indomethacin (IMC) molecules into self-assembled films of silica NPs (11-100 nm in diameter). Upon UV irradiation in ambient conditions, IMC degrades in a two-stage process. We demonstrate that nanoconfinement only enhances the photostability of IMC during stage 1, which primarily involves decarboxylation and oxidation. These reactions are kinetically limited by the diffusion of CO2 and O2 and are thus affected by the increased glass transition temperature, Tg, and viscosity under confinement. In contrast, during prolonged UV exposure in ambient conditions, stage 2 of IMC degradation, which involves further reactions with water, is unaffected by confinement. This is attributed to the availability of locally adsorbed water in the nanocomposite under ambient conditions, which does not rely on transport through the confined matrix. Overall, unlike previous reports in inert environments, IMC photodegradation in ambient conditions cannot be improved by confinement. These findings highlight the significance of specific degradation pathways in determining whether a material can be stabilized through extreme nanoconfinement.

The self-assembly of polyacrylic acid nanoparticles induced by non-covalent interactions enhances the response of molecular fluorescent probes to formaldehyde

Advanced visual colorimetric reagents and paper sensors have been developed by constructing a fluorescent supramolecular polymer architecture PAA@NBHN, to meet the requirements of environmental monitoring.

Self-assembled hyaluronic acid nanoparticles delivered by polymeric microneedles for targeted and long-acting therapy of psoriasis.

Psoriasis is an autoimmune-driven inflammatory skin disease, clinically characterized by skin thickening, erythema, and scaling, significantly impacting patients' life quality and mental health. Clinically, oral pill or injection of methotrexate (MTX) formulation is a common route for psoriasis therapy, while both methods often cause undesired toxicity due to systemic administration, and limit patient compliance because of the frequent-dosing requirement. Here, we introduce a dissolvable microneedle (MN) patch made of polyvinyl alcohol (PVA) that incorporates self-assembled hyaluronic acid (HA) nanoparticles (NPs) conjugating MTX, which is designed for treating skin diseases, offering reduced adverse effects and improved patient adherence through its targeted and long-acting properties. Upon transdermal delivery via polymeric MNs, the HA-based therapeutic NPs actively target to the inflammatory skin cells via the interaction of HA group with CD44 protein that is highly expressed on the cell membrane in the psoriatic skin. Moreover, the HA-based NPs undergo slow dissociation, thereby achieving sustained release of the MTX drug at the lesion site over 7days. Due to the favorite features, in the imiquimod (IMQ)-induced psoriatic mouse, only one application of the polymeric MN patch achieves diminished epidermal hyperplasia, and reduced inflammatory factors expression, ultimately improving the psoriasis-like skin condition in vivo.

A dendritic drug-drug conjugate self-assembled hypoxia-responsive supramolecular nanoparticle for combination therapy.

Hypoxia, a condition that enhances tumor invasiveness and metastasis, poses a significant challenge for diverse cancer therapies. There is a pressing demand for hypoxia-responsive nanoparticles with integrated photodynamic functions in order to address the aforementioned issues and overcome the reduced efficacy caused by tumor hypoxia. Here, we report a hypoxia-responsive supramolecular nanoparticle SN@IR806-CB consisting of a dendritic drug-drug conjugate (IR806-Azo-CB4) and anionic water-soluble [2]biphenyl-extended-pillar[6]arene modified with eight ammonium salt ions (AWBpP6) via the synergy of π-π stacking interaction, host-guest complexation, and hydrophobic interactions for synergistic photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy (CT; i.e., PTT-PDT-CT). Under near-infrared (NIR) irradiation, the IR806-based PTT and PDT could generate hyperthermia to thermally ablate tumor tissue and deplete oxygen to generate singlet oxygen (1O2), respectively. The resulting hypoxia exacerbation further accelerated the release of activated CB. Consequently, this nanoparticle could be a potential candidate for achieving significant therapeutic efficacy through PTT-PDT-CT.

Salicylaldimine-functionalized l-phenylalanine-based pseudopeptides: zinc-instructed conformational tuning of self-assembled nanostructures

Herein, zinc-instructed fluorescence turn-on and conformational tuning of self-assembled nanostructures of l-phenylalanine-based pseudopeptides are reported.

Magnetic field-assisted nanochain formation of intermixed catalytic Co-Pd nanoparticles.

Engineering on the nanoscale often involves optimizing performance by designing and creating new types of nanostructured materials. Multifunctional nanoparticles can be formed by combining elements that carry fundamentally different properties. The elements can be chosen based on the desired functionality, and by combining, e.g., magnetic, and catalytic elements, it is possible to self-assemble nanoparticles into catalytically active magnetic nanochains. However, mixing and assembling nanoparticles in a controlled way is challenging, and it is not obvious how the intermixing of the elements influences the properties of the individual nanoparticles. In this work, we synthesize and assemble intermixed magnetic and catalytic Cobalt-Palladium (Co-Pd) nanoparticles into multifunctional nanochains. The magnetic behavior is explored by studying the magnetic field-directed self-assembly of the nanoparticles into elongated nanochains. The catalytic properties are determined by measuring CO oxidation at elevated temperatures. Our results confirm that the magnetic and catalytic functionalities of the individual elements are retained when intermixed, which implies the potential to create nanochains with dual functionality that can be assembled in a controlled way.

Self-assembling nanoparticle vaccine elicits a robust protective immune response against avian influenza H5N6 virus in chickens

The continuous circulation and evolution of the H5N6 subtype highly pathogenic avian influenza virus (HPAIV) challenge the development of the global poultry industry and human public health security. To address the potential threat of the H5N6 virus, a secure and efficacious vaccine is urgent. In our research, a self-assembling nanoparticle vaccine presenting the hemagglutinin of the H5N6 AIV was developed based on the ferritin antigen display platform. The results showed that a single-dose vaccination of this nanoparticle vaccine elicited potent hemagglutination inhibition (HI) antibody responses and neutralizing antibody responses in the chickens. Meanwhile, the fused HA-ferritin nanoparticle vaccine induced significantly higher levels of Th1/Th2 immune responses. After a lethal attack with the H5N6 virus, the fused HA-ferritin nanoparticle vaccine conferred chickens with 100 % (10/10) challenge protection. Importantly, the fused HA-ferritin nanoparticle with only 28 hemagglutination units (HAU) provided chickens with immune protection comparable to commercial inactivated vaccines and protected the chickens from severe lung pathological damage. These results in our study support the superiority of ferritin as an antigen display platform and suggest that self-assembled nanoparticle vaccines based on this platform possess the potential as an avian influenza candidate vaccine.

Improving anti-oxidant stress treatment of subarachnoid hemorrhage through self-assembled nanoparticles of oleanolic acid

Subarachnoid hemorrhage (SAH) is a life-threatening acute hemorrhagic cerebrovascular disease, with early brain injury (EBI) being the main cause of high mortality and severe neurological dysfunction. Oxidative stress plays a crucial role in the pathogenesis of EBI. In this study, we synthesized antioxidant stress nanoparticles based on self-assembled oleanolic acid (OA) using the solvent volatilization method. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM) techniques were employed to analyze and understand the self-assembly mechanism of oleic acid nanoparticles (OA NPs). The TUNEL assay, Nissl staining, and brain water content measurements were conducted to investigate the impact of OA NPs on cortical neuronal injury. Additionally, Western blot analysis was performed to investigate the antioxidant stress mechanism of OA NPs. The result showed that OA NPs exhibited a spherical structure with an average diameter of 168 nm. The application of OA NPs in SAH has been found to contribute to the reduction of keap1 protein levels and an increase in the nuclear level of Nrf2. As a result, the transcription of antioxidant stress proteins, including HO1 and NQO1, is triggered. The activation of the antioxidant stress pathway by OA NPs ultimately leads to a decrease in neuron damage and an improvement in neurological dysfunction. In conclusion, we successfully designed and synthesized OA NPs that can efficiently target the site of SAH. These nanoparticles have demonstrated their potential as antioxidants for the treatment of SAH, offering significant clinical applications.

Spatiotemporal-controllable ROS-responsive camptothecin nano-bomb for chemo/photo/immunotherapy in triple-negative breast cancer

Chemotherapy is still one of the major approaches in triple-negative breast cancer (TNBC) treatment. The development of new formulations for classic chemotherapeutic drugs remains interests in studies. Camptothecin (CPT) is powerful antitumor agents in TNBC treatment though its clinic applications are limited by its low water solubility and systemic toxicity. To prepare a spatiotemporal controllable CPT nano-formulation, we construct a ROS-responsive self-assembly nanoparticle by combining hydrophobic CPT and hydrophilic 5-floxuridine (FUDR). A ROS-sensitive thioketal (TK) linker is used to prepare CPT-TK-FUDR (CTF). Next, we introduced IR780-based phototherapy to elicit massive ROS regeneration due to the endogenous ROS is not sufficient. IR780 is modified with hyaluronic acid (HA) to prepare HA-modified IR780 (HAIR) for its biocompatibility and tumor targeting ability improvement. CTF and HAIR self-assemble to form an attractive nano-bomb (HAIR/CTF NPs). HA accurately guides the NPs to tumor sites via HA-receptor recognition on tumor cells. After internalization, overexpressed intracellular HAase in tumor cells disassembles the NPs to free the contents. Due to the presence of IR780 molecules, the scheduled irradiation of 808 nm laser induces massive reactive oxygen species (ROS) generation, which further result in the cleavage of TK linker for free drugs release. Additionally, ROS-mediated photodynamic therapy (PDT) and near-infrared laser-mediated photothermal therapy (PTT) synergistically worked to eradicate tumor cells. Then immunogenic cell death (ICD) was evoked by CPT and phototherapy to amplify antitumor immunity, thereby achieving primary and abscopal tumor inhibition. In conclusion, the HAIR/CTF nano-bomb realized spatiotemporal controllable drug release, exciting tumor eradication and attractive anti-metastasis efficacy via combination chemo/photo/immunotherapy, offering a valuable reference for the re-development of classic drug in future clinical practice.Graphical

Neoantigen-Displaying Protein Nanoparticles as a Therapeutic Cancer Vaccine Against Melanoma.

Although interest in peptide-based cancer vaccines has surged in the era of personalized immunotherapy enabled by the discovery of neoantigens, the effective generation of neoantigen-specific T cell responses has been limited. Here, a Brucella BP26 protein-based nanoparticle displaying the MHC class II-restricted melanoma neoantigen, M30, is reported for use as a therapeutic cancer vaccine. Genetic engineering of 10 tandem repeats of the M30 neoepitope to a BP26 monomer results in the self-assembled, neoantigen-displaying protein nanoparticles (BP26-M30 NPs). Subcutaneous immunization of mice with BP26-M30 NPs/CpG adjuvant leads to the activation and maturation of antigen-presenting cells in draining local lymph nodes and elicits M30-specific CD4+ T cell immune responses and immunological memory. In a mouse model of aggressive B16-F10 melanoma, immunization with BP26-M30 NPs/CpG significantly inhibits the growth of established tumors. These findings suggest that the BP26-based self-assembled protein nanoparticle has the potential to be used as a cancer vaccine platform for personalized cancer immunotherapy.

Computational design of bifaceted protein nanomaterials.

Recent advances in computational methods have led to considerable progress in the design of self-assembling protein nanoparticles. However, nearly all nanoparticles designed to date exhibit strict point group symmetry, with each subunit occupying an identical, symmetrically related environment. This limits the structural diversity that can be achieved and precludes anisotropic functionalization. Here, we describe a general computational strategy for designing multi-component bifaceted protein nanomaterials with two distinctly addressable sides. The method centers on docking pseudosymmetric heterooligomeric building blocks in architectures with dihedral symmetry and designing an asymmetric protein-protein interface between them. We used this approach to obtain an initial 30-subunit assembly with pseudo-D5 symmetry, and then generated an additional 15 variants in which we controllably altered the size and morphology of the bifaceted nanoparticles by designing de novo extensions to one of the subunits. Functionalization of the two distinct faces of the nanoparticles with de novo protein minibinders enabled specific colocalization of two populations of polystyrene microparticles coated with target protein receptors. The ability to accurately design anisotropic protein nanomaterials with precisely tunable structures and functions could be broadly useful in applications that require colocalizing two or more distinct target moieties.

Hydrogel-Assisted Robust Supraparticles Evolved from Droplet Evaporation.

Supraparticles, formed through the self-assembly of nanoparticles, are promising contenders in catalysis, sensing, and drug delivery due to their exceptional specific surface area and porosity. However, their mechanical resilience, especially in dimensions spanning micrometers and beyond, is challenged by the inherently weak interactions among their constituent building blocks, significantly constraining their broad applicability. Here, we have exploited a robust supraparticle fabrication strategy by integrating hydrogel components into the assembly system and evaporating on the superamphiphobic surface. The resultant SiO2/SA (sodium alginate) supraparticles, achieved by evaporating a 15% volume fraction dispersion of SiO2 nanoparticles containing 18.46 mg/mL of sodium alginate and subsequently cross-linking with Ca2+, demonstrate mechanical robustness with a fracture force of 6.04 N, representing a mechanical strength enhancement of 60 times higher than that prior to the incorporation of the hydrogel component. The supraparticles maintain their original morphology after 30 min of ultrasonic treatment (200 W), demonstrating mechanical stability. This method exhibits generalizability, enabling the customization of supraparticles with various building blocks and hydrogel backbone materials. Based on such a methodology, we have synthesized enzyme-carrying supraparticles, further expanding the potential applications in intricate cascade reactions. The encapsulated glucose oxidase and horseradish peroxidase maintained their inherent reactivity, and such hydrogel-assisted robust supraparticles exhibited exceptional performance in accurate glucose assays, indicating great practical application in biocatalysis.