Nanoscale Self-assembly Research Articles

Novel Chiral Self-Assembled Nano-Fluorescence Materials with AIE Characteristics for Specific Enantioselective Recognition of L-Lysine.

In this paper, two aggregation-induced emission (AIE) chiral fluorescent materials, S-1 and S-2, were synthesized. The two materials are based on BINOL and H8-BINOL backbones, respectively, and large electron-absorbing groups are attached to the chiral backbones through the Knoevenagel reaction. At the same time, the CD signals of these two chiral fluorescent materials are gradually weakened (fw gradually increases) as they continue to aggregate. However, S-2 underwent a flip-flop from a negative to positive chiral CD signal at fw ≥ 90. And both materials also showed significant enantioselective recognition of lysine, demonstrating their potential as novel chiral fluorescent probes. Among them, the enantioselective fluorescence enhancement ratios (ef) of S-1 and S-2 for lysine were 10.0 and 10.3, respectively, while different degrees of blue shifts were produced by the ICT mechanism during the recognition process. In addition, the self-assembled morphology of the two nanomaterials is different; S-1 comprises hollow-core vesicles that are more likely to aggregate to form larger self-assembled vesicles, whereas S-2 is a solid block structure. When L/D-lysine was added alone, the morphology of S-1 was more distinctly different compared to S-2. With the addition of L-lysine, S-1 was dispersed and regularly spherical, whereas with the addition of D-lysine, S-1 itself remained in the form of aggregated large vesicles. This suggests that both S-1 and S-2 are important in the fields of chiral optics, chiral recognition, and nanoscale self-assembly.

Rheological and mechanical comparison of di-and tri-block copolymer imine vitrimers

Vitrimers’ tendency to creep over time under stress poses a significant challenge to their widespread industrial use. Recently, nanoscale self-assembly has emerged as a promising route to control creep in vitrimers; however, mechanical robustness of such phase-separated materials requires further enhancement and investigation. Herein, we explored how the prepolymer architecture influences the structure-property relationships in vitrimers made of statistical copolymers, AB hard-soft diblock copolymers, and ABA hard-soft-hard triblock copolymers. Reversible addition fragmentation chain-transfer (RAFT) polymerization was employed to control the length, sequence, and morphology of the precursors. Dynamic imine functionalities were localized within the soft segment, which consisted of a bio-based copolymer of long-chain alkyl methacrylate and aldehyde-functional vanillin methacrylate. Compared to the statistical vitrimers, the triblock copolymer vitrimers exhibited approximately 60 % improved creep resistance, a 400 % increase in hardness, a higher tensile modulus, and ∼ 57 % higher stress at break. In contrast, vitrimers derived from diblock copolymers exhibited much weaker tensile properties with approximately 30 % lower stress at break. Our findings suggest that by controlling the chain architecture in block copolymers and optimizing the order–disorder transition, we can enhance vitrimers’ creep resistance and tune their viscoelastic properties while tailoring their mechanical strength.

Antibody-Directing Antibody Conjugates (ADACs) Enabled by Orthogonal Click Chemistry for Targeted Intracellular Delivery.

Using orthogonal click chemistries for efficient nanoscale self-assembly, a new antibody-directing antibody conjugate (ADAC) nanogel is generated. In this system, one of the antibodies is displayed on the nanogel surface to specifically recognize cell-surface epitopes while the other antibody is encapsulated inside the nanogel core. The system is programmed to release the latter antibody in its functional form in the cytosolic environment of a specific cell to engage intracellular targets. ADACs offer a potential solution to harness the advantages seen with antibody-drug conjugates (ADCs) to deliver therapeutic cargos to specific tissues, but with the added capability of carrying biologics as the cargo. In this manuscript, this potential is demonstrated through delivery of antibodies against intracellular targets in specific cells. This platform offers new avenues for precise therapeutic interventions and the potential to address previously "undruggable" cellular targets.

Harnessing Polar Interactions Tunes the Stability of Ultrathin Polymer Solution Films.

The stability of ultrathin (<100 nm) polymer films is essential in applications like protective coatings. On the contrary, their instability may actually be desirable for the emergence of self-assembled nanoscale patterns utilized in the fabrication of functional devices. Polymer solution films exhibit two distinct kinds of instabilities, viz., dewetting (long-wave) and decomposition (short-wave). Dewetting refers to the rupture of the continuous film to form isolated domains, while decomposition leads to phase separation within the polymer solution. The focus of this work is on leveraging polar interactions between the solute and solvent molecules to tune the stability of the film. A gradient dynamics-based thin film model is developed to investigate pattern formation in a thin polar polymer solution film. The Flory-Huggins theory is suitably modified by introducing a polar interaction parameter that depends upon the concentration of the polymer and the dipole moments of monomer (μ1) and solvent molecules (μ0). A linear stability analysis is performed to determine the characteristic length scale and growth rate of the instabilities. It is shown that the range of concentration space for the occurrence of the decomposition mode is directly affected by the Flory interaction parameter (χ0), μ0, and μ1, thereby serving as control parameters to tune the width of the concentration range. It is further shown that ignoring polar interactions may lead to incorrect predictions of the instability mode, including a complete loss of the decomposition mode. In addition, the long-wave dewetting length scale is found to decrease due to bulk dipolar interactions at higher polymer concentrations. Finally, numerical simulations are carried out to track the nonlinear evolution of the interface and concentration field for both the decomposition and dewetting modes of instability.

AuBr3 Induces CsPb(Br/I)3 QDs to Self-Assemble into Nanowires.

Perovskite quantum dots can form various forms such as nanowires, nanorods, and nanosheets through self-assembly. Nanoscale self-assembly can be used to fabricate materials with excellent device properties. This study introduces AuBr3 into CsPb(Br/I)3 quantum dots, causing them to assemble into nanowires. The nanowires form because part of Au3+ is surface-doped to replace Pb2+, and the [PbX6]4- octahedral structure is distorted. The symmetry of the structural surface is broken, and a dipole-moment-induced field is generated, thus promoting self-assembly. Moreover, the presence of Au nanoparticles (NPs) causes a localized surface plasmon resonance and generates strong van der Waals forces that promote self-assembly. Finally, to test other applications of perovskite nanowires, the solution method is used to prepare films by compounding the sample solution and polystyrene (PS) for backlighted displays.

DNA-Templated Nanofabrication of CdS-Au Nanoscale Schottky Contacts and Electrical Characterization.

DNA-templated nanofabrication presents an innovative approach to creating self-assembled nanoscale metal-semiconductor-based Schottky contacts, which can advance nanoelectronics. Herein, we report the successful fabrication of metal-semiconductor Schottky contacts using a DNA origami scaffold. The scaffold, consisting of DNA strands organized into a specific linear architecture, facilitates the competitive arrangement of Au and CdS nanorods, forming heterojunctions, and addresses previous limitations in low electrical conductance making DNA-templated electronics with semiconductor nanomaterials. Electroless gold plating extends the Au nanorods and makes the necessary electrical contacts. Tungsten electrical connection lines are further created by electron beam-induced deposition. Electrical characterization reveals nonlinear Schottky barrier behavior, with electrical conductance ranging from 0.5 × 10-4 to 1.7 × 10-4 S. The conductance of these DNA-templated junctions is several million times higher than with our prior Schottky contacts. Our research establishes an innovative self-assembly approach with applicable metal and semiconductor materials for making highly conductive nanoscale Schottky contacts, paving the way for the future development of DNA-based nanoscale electronics.

An intelligent and self-assembled nanoscale metal organic framework (99mTC-DOX loaded Fe3O4@FeIII-tannic acid) for tumor targeted chemo/chemodynamic theranostics

BackgroundRecent advances in clinical transformation research have focused on chemodynamic theranostics as an emerging strategy for tackling cancer. Nevertheless, its effectiveness is hampered by the tumor's glutathione antioxidant effect, poor acidic tumor microenvironment (TME) and inadequate endogenous H2O2. Hence, we designed an activatable theranostics (99mTc-DOX loaded AA-Fe3O4@FeIII-TA) that effectively boost the catalytic efficiency of the Fenton-reaction-induced ROS production and augment the chemotherapeutic efficacy combined with diagnostic action.ResultsA cross-linked matrix of tannic acid-ferric salt (FeIII-TA) as a pH-responsive shell onto ascorbic acid-decorated iron-oxide nanoparticles (AA-Fe3O4NPs) was prepared demonstrating a metal–organic- framework (MOF) nanostructure, followed by loading of 99mTc-labelled DOX. The platform (99mTc-DOX loaded AA-Fe3O4@FeIII-TA) displayed suitable physical–chemical properties, including 69.8 nm particle size, 94.8 nm hydrodynamic size, − 21 mV zeta potential, effective FeIII-TA shell crosslinking onto AA-Fe3O4NPs and 94% loading efficiency for 99mTc-DOX. The results of the in-vitro release investigations showed that the platform exhibited a pH-dependent release manner with 98.3% of the 99mTc-DOX being released at pH 5 (simulating the tumor’s pH) and only 10% being released at the physiological pH (pH 7.4). This indicates that there was negligible payload leakage into the systemic circulation during the platform's passive accumulation inside tumor. Due to the acidic TME nature, the MOF shell might be degraded releasing free FeIII, TA and a sustained release of 99mTc-DOX. Besides its chemotherapeutic impact and capacity to raise intracellular H2O2 content, the released 99mTc-DOX might be used as SPECT imaging tracer for concurrent tumor diagnosis. Furthermore, the mild acidity of the tumor may be overcome by the released TA, which might raise the acidification level of cancer cells. The released FeIII, TA and the endogenous GSH could engage in a redox reaction that depletes GSH and reduces FeIII to FeII ions which subsequently catalyze the elevated concentration of H2O2 to reactive •OH via Fenton-like reaction, increasing the effectiveness of chemodynamic therapy. Moreover, the in-vivo evaluation in tumor-bearing mice showed significant radioactivity accumulation in the tumor lesion (16.8%ID/g at 1 h post-injection) with a potential target/non-target ratio of 8.ConclusionsThe 99mTc-DOX loaded AA-Fe3O4@FeIII-TA could be introduced as an effective chemo/chemodynamic theranostics.Graphical

Role of Unimers to Polymersomes Transition in Pluronic Blends for Controlled and Designated Drug Conveyance.

This study investigates the nanoscale self-assembly from mixtures of two symmetrical poly(ethylene oxide)-poly(propylene oxide)-pol(ethylene oxide) (PEO-PPO-PEO) block copolymers (BCPs) with different lengths of PEO blocks and similar PPO blocks. The blended BCPs (commercially known as Pluronic F88 and L81, with 80 and 10% PEO, respectively) exhibited rich phase behavior in an aqueous solution. The relative viscosity (ηrel) indicated significant variations in the flow behavior, ranging from fluidic to viscous, thereby suggesting a possible micellar growth or morphological transition. The tensiometric experiments provided insight into the intermolecular hydrophobic interactions at the liquid-air interface favoring the surface activity of mixed-system micellization. Dynamic light scattering (DLS) and small-angle neutron scattering (SANS) revealed the varied structural morphologies of these core-shell mixed micelles and polymersomes formed under different conditions. At a concentration of ≤5% w/v, Pluronic F88 exists as molecularly dissolved unimers or Gaussian chains. However, the addition of the very hydrophobic Pluronic L81, even at a much lower (<0.2%) concentration, induced micellization and promoted micellar growth/transition. These results were further substantiated through molecular dynamics (MD) simulations, employing a readily transferable coarse-grained (CG) molecular model grounded in the MARTINI force field with density and solvent-accessible surface area (SASA) profiles. These findings proved that F88 underwent micellar growth/transition in the presence of L81. Furthermore, the potential use of these Pluronic mixed micelles as nanocarriers for the anticancer drug quercetin (QCT) was explored. The spectral analysis provided insight into the enhanced solubility of QCT through the assessment of the standard free energy of solubilization (ΔG°), drug-loading efficiency (DL%), encapsulation efficiency (EE%), and partition coefficient (P). A detailed optimization of the drug release kinetics was presented by employing various kinetic models. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] MTT assay, a frequently used technique for assessing cytotoxicity in anticancer research, was used to gauge the effectiveness of these QCT-loaded mixed nanoaggregates.

Nanoparticle-reinforced SiOC ceramic matrix composite films with structure gradient fabricated by inkjet printing and laser sintering

Ceramic matrix composites (CMCs) play an important role in various load-bearing applications. However, fabricating CMCs with both high toughness and stiffness, which are normally mutually exclusive properties, is challenging. Here, we develop an SiOC composite film reinforced with nanoscale tungsten-based particles with a structure and property gradient by integrating hybrid nanoparticle inkjet printing and selective laser sintering. Mechanical results of the resulting SiOC-WOx films exhibit a stiffness-toughness co-enhancement, including a 2-fold improvement in hardness and modulus, and a 3.8-fold better fracture toughness than the matrix material. Moreover, the films exhibit interfacial bonding strengths of up to 86.6 MPa and operate stably at 1050 °C. This performance is attributed to a gradient in the metal-to-ceramic composition and uniformly dispersed self-assembled nanoscale reinforcing particles. This nanoparticle laser sintering method could be used to prepare other materials with structure and property gradients.

No free lunch for avoiding clustering vulnerabilities in distributed systems

Emergent design failures are ubiquitous in complex systems, and often arise when system elements cluster. Approaches to systematically reduce clustering could improve a design’s resilience, but reducing clustering is difficult if it is driven by collective interactions among design elements. Here, we use techniques from statistical physics to identify mechanisms by which spatial clusters of design elements emerge in complex systems modelled by heterogeneous networks. We find that, in addition to naive, attraction-driven clustering, heterogeneous networks can exhibit emergent, repulsion-driven clustering. We draw quantitative connections between our results on a model system in naval engineering to entropy-driven phenomena in nanoscale self-assembly, and give a general argument that the clustering phenomena we observe should arise in many distributed systems. We identify circumstances under which generic design problems will exhibit trade-offs between clustering and uncertainty in design objectives, and we present a framework to identify and quantify trade-offs to manage clustering vulnerabilities.

Experimental Demonstration of Reservoir Computing with Self-Assembled Percolating Networks of Nanoparticles.

The complex self-assembled network of neurons and synapses that comprises the biological brain enables natural information processing with remarkable efficiency. Percolating networks of nanoparticles (PNNs) are complex self-assembled nanoscale systems that have been shown to possess many promising brain-like attributes and which are therefore appealing systems for neuromorphic computation. Here experiments are performed that show that PNNs can be utilized as physical reservoirs within a nanoelectronic reservoir computing framework and demonstrate successful computation for several benchmark tasks (chaotic time series prediction, nonlinear transformation, and memory capacity). For each task, relevant literature results are compiled and it is shown that the performance of the PNNs compares favorably to that previously reported from nanoelectronic reservoirs. It is then demonstrated experimentally that PNNs can be used for spoken digit recognition with state-of-the-art accuracy. Finally, a parallel reservoir architecture is emulated, which increases the dimensionality and richness of the reservoir outputs and results in further improvements in performance across all tasks.

High performance self-assembled sulfidized nanoscale zero-valent iron for the immobilization of cadmium in contaminated sediments: Optimization, microbial response, and mechanisms

Sulfidized nanoscale zero-valent iron (S-nZVI) showed excellent removal capacity for cadmium (Cd) in aqueous phase. However, the remediation effects of S-nZVI on Cd-contaminated sediment and its interactions with microorganisms in relation to Cd fate remain unclear. The complexity of the external environment posed a challenge for Cd remediation. This study synthesized S-nZVI with different S and Fe precursors to investigate the effect of precursors and applied the optimal material to immobilize Cd in sediments. Characterization analysis revealed that the precursor affected the morphology, Fe0 crystallinity, and the degree of oxidation of the material. Incubation experiments demonstrated that the immobilization efficiency of Cd using S-nZVIFe3++S2- (S/Fe = 0.14) reached the peak value of 99.54%. 1% and 5% dosages of S-nZVI significantly reduced Cd concentration in the overlying water, DTPA-extractable Cd content, and exchangeable (EX) Cd speciation (P < 0.05). Cd leaching in sediment and total iron in the overlying water remained at low levels during 90 d of incubation. Notably, each treatment maintained a high Cd immobilization efficiency under different pH, water/sediment ratio, organic acid, and coexisting ion conditions. Sediment physicochemical properties, functional bacteria, and a range of adsorption, complexation and precipitation of CdS effects dominated Cd immobilization.

Self-assembled Janus base nanotubes: chemistry and applications.

Janus base nanotubes are novel, self-assembled nanomaterials. Their original designs were inspired by DNA base pairs, and today a variety of chemistries has developed, distinguishing them as a new family of materials separate from DNA origami, carbon nanotubes, polymers, and lipids. This review article covers the principal examples of self-assembled Janus base nanotubes, which are driven by hydrogen-bond and π-π stacking interactions in aqueous environments. Specifically, self-complementary hydrogen bonds organize molecules into ordered arrays, forming macrocycles, while π-π interactions stack these structures to create tubular forms. This review elucidates the molecular interactions that govern the assembly of nanotubes and advances our understanding of nanoscale self-assembly in water.

Self-assembled nanoscale entities: Preparative process optimization, payload release, and enhanced bioavailability of thymoquinone natural product

Abstract Thymoquinone (TMQ), present in Nigella sativa L., exhibits antioxidant, anti-inflammatory, and anti-apoptotic properties. Poor aqueous solubility, low oral bioavailability, hepatic first-pass metabolic constraints, and pH instability have limited TMQ’s in vivo use in clinical settings. This study designed and prepared thermodynamically stable, self-emulsified, nanoscale vesicles with the ternary diagram assistance to produce self-nanoemulsifying drug delivery system (SNEDDS). The TMQ-SNEDDS preparations used clove oil, isopropyl myristate (IPM) (1:1), Labrasol, and Transcutol-P. The SNEDDS mean droplet size varied between 72.85 and 98.42 nm, and approximately &gt;70% TMQ was released within the first 4 h. The peak plasma concentration values of TMQSNE3 and TMQ suspension were 420.31 ± 35.23 and 98.51 ± 9.97 μg/mL, respectively, whereas time to achieve the peak plasma concentration values were 0.75 ± 0.12 and 1.0 ± 0.30 h, respectively. The area under the curve from time 0 to t (AUC0–t ) and the area under the moment curve from time 0 to t (AUMC0–t ) of TMQSNE3 were found to be 1838.63 ± 55.73 µg h/mL and 1909.59 ± 382.81 µg h/mL, respectively, which were highly significant (p &lt; 0.05) in comparison with AUC0–t (389.36 ± 87.08 μg h/mL) and AUMC0–t (390.31 ± 184.55 μg h/mL) of the TMQ suspension. The relative bioavailability of TMQ was enhanced by 4.7-folds for the optimized TMQSNEDDS than that of the free drug suspension. The SNEDDS enhanced the bioavailability, which, in turn, positively affected the therapeutic efficacy of this naturally bioactive compound, TMQ, which has delivery and bioavailability problems owing to poor aqueous solubility.

Modulating hierarchical self-assembly in thermoresponsive intrinsically disordered proteins through high-temperature incubation time

The cornerstone of structural biology is the unique relationship between protein sequence and the 3D structure at equilibrium. Although intrinsically disordered proteins (IDPs) do not fold into a specific 3D structure, breaking this paradigm, some IDPs exhibit large-scale organization, such as liquid–liquid phase separation. In such cases, the structural plasticity has the potential to form numerous self-assembled structures out of thermal equilibrium. Here, we report that high-temperature incubation time is a defining parameter for micro and nanoscale self-assembly of resilin-like IDPs. Interestingly, high-resolution scanning electron microscopy micrographs reveal that an extended incubation time leads to the formation of micron-size rods and ellipsoids that depend on the amino acid sequence. More surprisingly, a prolonged incubation time also induces amino acid composition-dependent formation of short-range nanoscale order, such as periodic lamellar nanostructures. We, therefore, suggest that regulating the period of high-temperature incubation, in the one-phase regime, can serve as a unique method of controlling the hierarchical self-assembly mechanism of structurally disordered proteins.

Multiresponsive Nanoscale Self-Assembly of Azurin-Elastin-like Polypeptide Fusion Protein for Enhanced Prostate Cancer Therapy.

A fusion protein composed of a bacterial protein, azurin, having antineoplastic properties and a thermally responsive structural cationic elastin-like protein (ELP), is designed, cloned, expressed, and purified. A simple method of inverse transition cycle (ITC) is employed to purify the fusion protein azurin-ELP diblock copolymer (d-bc). The molecular weight of the azurin-ELP fusion protein is ∼32 kDa. Further, its self-assembly properties are investigated. Interestingly, the engineered azurin-ELP d-bc in response to increasing temperature shows a dual-step phase separation into biofunctional nanostructures. Around the physiological temperature, azurin-ELP d-bc forms stable coacervates, which is dependent on the concentration and time of incubation. These coacervates are formed below the lower critical solubility temperature (LCST) of the ELP block at physiological temperature. Above LCST, i.e., 50-55°C, micelles of size ranging from 25 to 30 nm are formed. The cytotoxicity of azurin-ELP d-bc depends on the size of the coacervates formed and their cellular uptake at physiological temperature. Further, MTT assay of azurin-ELP d-bc in the cross-linked micelles prepared ex situ shows > six times higher killing of LNCaP cells than the unimeric form of azurin-ELP at 5 μM concentration. The flow cytometric results of these micelles at 20 μM concentration show ∼97% LNCaP cells in the apoptotic phase. Thus, azurin-ELP cross-linked micelles have enhanced potential for anticancer therapy due to their higher avidity.

Nanoscale Self-Assemblies from Amphiphilic Block Copolymers as Proficient Templates in Drug Delivery

This review article emphasizes the current enlargements in the formation and properties of the various nanostructured aggregates resulting from the self-assembly of a variety of block copolymers (BCPs) in an aqueous solution. The development of the different polymerization techniques which produce polymers with a desired predetermined molecular weight and low polydispersity is investigated with regard to their technological and biomedical applications; in particular, their applications as vehicles for drug delivery systems are considered. The solution behavior of amphiphilic BCPs and double-hydrophilic block copolymers (DHBCs), with one or both blocks being responsive to any stimulus, is discussed. Polyion complex micelles (PICMs)/polymersomes obtained from the electrostatic interaction of a polyelectrolyte-neutral BCP with oppositely charged species are also detailed. Lastly, polymerization-induced self-assembly (PISA), which forms nanoscale micellar aggregates with controlled size/shape/surface functionality, and the crystallization-driven self-assembly of semicrystalline BCPs facilitated when one block of the BCP is crystallizable, are also revealed. The scalability of the copolymeric micelles in the drug delivery systems and pharmaceutical formations that are currently being used in clinical trials, research, or preclinical testing is emphasized as these micelles could be used in the future to create novel nanomedicines. The updated literature and the future perspectives of BCP self-assembly are considered.

Development of Self-Assembled Biomimetic Nanoscale Collagen-like Peptide-Based Scaffolds for Tissue Engineering: An In Silico and Laboratory Study.

Development of biocomposite scaffolds has gained tremendous attention due to their potential for tissue regeneration. However, most scaffolds often contain animal-derived collagen that may elicit an immunological response, necessitating the development of new biomaterials. Herein, we developed a new collagen-like peptide,(Pro-Ala-His)10 (PAH)10, and explored its ability to be utilized as a functional biomaterial by incorporating it with a newly synthesized peptide-based self-assembled gel. The gel was prepared by conjugating a pectin derivative, galataric acid, with a pro-angiogenic peptide (LHYQDLLQLQY) and further functionalized with a cortistatin-derived peptide, (Phe-Trp-Lys-Thr)4 (FWKT)4, and the bio-ionic liquid choline acetate. The self-assembly of (PAH)10 and its interactions with the galactarate-peptide conjugates were examined using replica exchange molecular dynamics (REMD) simulations. Results revealed the formation of a multi-layered scaffold, with enhanced stability at higher temperatures. We then synthesized the scaffold and examined its physicochemical properties and its ability to integrate with aortic smooth muscle cells. The scaffold was further utilized as a bioink for bioprinting to form three-dimensional cell-scaffold matrices. Furthermore, the formation of actin filaments and elongated cell morphology was observed. These results indicate that the (PAH)10 hybrid scaffold provides a suitable environment for cell adhesion, proliferation and growth, making it a potentially valuable biomaterial for tissue engineering.

High-Affinity Host-Guest Recognition for Efficient Assembly and Enzymatic Responsiveness of DNA Nanostructures.

The combination of multiple orthogonal interactions enables hierarchical complexity in self-assembled nanoscale materials. Here, efficient supramolecular polymerization of DNA origami nanostructures is demonstrated using a multivalent display of small molecule host-guest interactions. Modification of DNA strands with cucurbit[7]uril (CB[7]) and its adamantane guest, yielding a supramolecularcomplex with an affinity of order 1010 m-1 , directs hierarchical assembly of origami monomers into 1D nanofibers. This affinity regime enables efficient polymerization; a lower-affinity β-cyclodextrin-adamantane complex does not promote extended structures at a similar valency. Finally, the utility of the high-affinity CB[7]-adamantane interactions is exploited to enable responsive enzymatic actuation of origami nanofibers assembled using peptide linkers. This work demonstrates the power of high-affinity CB[7]-guest recognition as an orthogonal axis to drive self-assembly in DNA nanotechnology.

Encapsulation of an Antioxidant in Redox-Sensitive Self-Assembled Albumin Nanoparticles for the Treatment of Hepatitis.

Hepatitis is an inflammation of the liver caused by the inadequate elimination of reactive oxygen species (ROS) derived from Kupffer cells. Edaravone is clinically used as an antioxidant but shows poor liver distribution. Herein, we report on the design of a Kupffer cell-oriented nanoantioxidant based on a disulfide cross-linked albumin nanoparticle containing encapsulated edaravone (EeNA) as a therapeutic for the treatment of hepatitis. Since the edaravone is bound to albumin, this results in a soluble and stable form of edaravone in water. Exchanging the intramolecular disulfide bonds to intermolecular disulfide bridges of albumin molecules allowed the preparation of a redox responsive albumin nanoparticle that is stable in the blood circulation but can release drugs into cells. Consequently, EeNA was fabricated by the nanoscale self-assembly of edaravone and albumin nanoparticles without the additives that are contained in commercially available edaravone preparations. EeNA retained its nanostructure under serum conditions, but the encapsulated edaravone was released efficiently under intracellular reducing conditions in macrophages. The EeNA was largely distributed in the liver and subsequently internalized into Kupffer cells within 60 min after injection in a concanavalin-A-induced hepatitis mouse. The survival rate of the hepatitis mice was significantly improved by EeNA due to the suppression of liver necrosis and oxidative stress by scavenging excessive ROS. Moreover, even through the postadministration, EeNA showed an excellent hepatoprotective action as well. In conclusion, EeNA has the potential for use as a nanotherapeutic against various types of hepatitis because of its Kupffer cell targeting ability and redox characteristics.