Self-assembled Systems Research Articles

Self-assembled lyotropic liquid crystals from natural surfactant: A study on their structural, rheological and antimicrobial behaviour

Soft self-assembled systems with smart functions have been explored over the past decades for diverse applications. However, the toxicity of synthetic surfactant based self-assembled systems and their stability always remain a point of concern. There is always a great quest to find an alternative to overcome such shortcomings of self-assembled systems. Hence, in this context, we made an effort to engineer self-assembled lyotropic liquid crystals (LLCs) using different concentrations of the medicinal plant Glycyrrhiza glabra L. in the nonaqueous polar media of glycerol, ethylene glycol and formamide. These nonaqueous solvents with considerable polarity, high cohesive energy, dipole moment and hydrogen bonding ability, not only offer the perfect environment for self-assembly, but also provide longtime stability. Nematic lyotropic ordering is obtained for studied systems at different concentrations of Glycyrrhiza glabra L./ nonaqueous solvents as confirmed via polarising optical microscopy (POM) and X-ray diffraction (XRD) analysis. Electrostatic and hydrogen bonding interactions among polar solvents and amphiphilic Glycyrrhiza glabra L. molecules could be responsible for nematic ordering. FTIR spectroscopy is employed to confirm the hydrogen bonding in LLCs. The prepared LLCs are studied through static, dynamic rheology under the shear range 1–100 s-1 to explore their fluidic behaviour and establish correlation with structural parameters. The studied LLC systems from three solvents exhibit non-Newtonian shear thinning behaviour at all concentrations. The dynamic rheology tests indicate the elastic behaviour of all LLC systems. LLCs derived from glycerol exhibit soft-solid gel-like behaviour, while weak gel-type behaviour is observed for ethylene glycol and formamide-based LLCs. Considering the medicinal value of prepared LLCs, their antibacterial activity has been checked against the gram-positive bacteria Bacillus subtilis. LLC phases show strong antibacterial activity, about 2–3 times better than that of the standard drug streptomycin used for this study.

Crystallization inhibition and enhanced release of nobiletin in supramolecular peptide assemblies

To address the challenges associated with the crystallization tendency of natural bioactive drugs, we propose a strategy for encapsulating a model hydrophobic medicine, Nobiletin (NOB), using the self-assembly system formed by a peptide amphiphile C16-KVK-CONH2 (KVK). The experimental results demonstrate that at low concentrations, KVK forms micelles that can effectively encapsulate NOB molecules and significantly inhibit their crystallization. As the concentration increases, KVK self-assembles into a fibrous hydrogel, further enhancing the inhibition of NOB crystallization. In vitro release experiments reveal that NOB encapsulated by KVK exhibits superior release performance. When compared to traditional surfactants, KVK demonstrates better inhibitory effects on NOB crystallization, maintaining stability over a prolonged period, indicating its potential for hydrophobic drug delivery applications.

Quantifying the Microstructure of Dried Deposits Using Height-Height Correlation Function.

Colloidal self-assembly has garnered significant attention in recent research, owing to applications in medical and engineering domains. Understanding the arrangement of particles in self-assembled systems is crucial for comprehending the underlying physics and synthesizing complex nano- and microscale structures. In this study, we introduce a novel methodology for analyzing the spatial distribution of particles in colloidal assemblies, focusing specifically on quantifying the microstructure of deposits formed by the evaporation of colloidal particle-laden drops. Utilizing a height-height correlation-function-based approach, we quantify variations in the height profile of deposits in radial and azimuthal directions. This approach enables the classification of the patterns into typical examples encountered in an evaporation-driven assembly. The method is demonstrated to be robust for quantifying synthetic and experimentally obtained deposit patterns, exhibiting excellent agreement in the estimated parameters. The mapping developed between pattern morphology and the quantitative measures introduced in this work may be used in a variety of applications including disease diagnosis as well as in developing pattern recognition tools.

Deep eutectic solvent self-assembled reverse nanomicelles for transdermal delivery of sparingly soluble drugs

BackgroundTransdermal delivery of sparingly soluble drugs is challenging due to their low solubility and poor permeability. Deep eutectic solvent (DES)/or ionic liquid (IL)-mediated nanocarriers are attracting increasing attention. However, most of them require the addition of auxiliary materials (such as surfactants or organic solvents) to maintain the stability of formulations, which may cause skin irritation and potential toxicity.ResultsWe fabricated an amphiphilic DES using natural oxymatrine and lauric acid and constructed a novel self-assembled reverse nanomicelle system (DES-RM) based on the features of this DES. Synthesized DESs showed the broad liquid window and significantly solubilized a series of sparingly soluble drugs, and quantitative structure-activity relationship (QSAR) models with good prediction ability were further built. The experimental and molecular dynamics simulation elucidated that the self-assembly of DES-RM was adjusted by noncovalent intermolecular forces. Choosing triamcinolone acetonide (TA) as a model drug, the skin penetration studies revealed that DES-RM significantly enhanced TA penetration and retention in comparison with their corresponding DES and oil. Furthermore, in vivo animal experiments demonstrated that TA@DES-RM exhibited good anti-psoriasis therapeutic efficacy as well as biocompatibility.ConclusionsThe present study offers innovative insights into the optimal design of micellar nanodelivery system based on DES combining experiments and computational simulations and provides a promising strategy for developing efficient transdermal delivery systems for sparingly soluble drugs.

Activating Iterative Revolutions of the Cancer-Immunity Cycle in Hypoxic Tumors with a Smart Nano-Regulator.

The activation of sequential events in the cancer-immunity cycle (CIC) is crucial for achieving effective antitumor immunity. However, formidable challenges, such as innate and adaptive immune resistance, along with the off-target adverse effects of nonselective immunomodulators, persist. In this study, a tumor-selective nano-regulator named PNBJQ has been presented, focusing on targeting two nonredundant immune nodes: inducing immunogenic cancer cell death and abrogating immune resistance to fully activate endogenous tumor immunity. PNBJQ is obtained by encapsulating the immunomodulating agent JQ1 within a self-assembling system formed by linking a Type-I photosensitizer to polyethylene glycol through a hypoxia-sensitive azo bond. Benefiting from the Type-I photosensitive mechanism, PNBJQ triggers the immunogenic cell death of hypoxic tumors under near-infrared (NIR)light irradiation. This process resolves innate immune resistance by stimulating sufficient cytotoxic T-lymphocytes. Simultaneously, PNBJQ smartly responds to the hypoxic tumor microenvironment for precise drug delivery, adeptly addressing adaptive immune resistance by using JQ1 to downregulate programmed death ligand 1 (PD-L1) and sustaining the response of cytotoxic T lymphocytes. The activatable synergic photoimmunotherapy promotes an immune-promoting tumor microenvironment by activating an iterative revolution of the CIC, which remarkably eradicates established hypoxic tumors and suppresses distal lesions under low light dose irradiation.

Transformation of a Viral Capsid from Nanocages to Nanotubes and Then to Hydrogels: Redirected Self-Assembly and Effects on Immunogenicity.

The ability to manipulate the self-assembly of proteins is essential to understanding the mechanisms of life and beneficial to fabricating advanced nanomaterials. Here, we report the transformation of the MS2 phage capsid from nanocages to nanotubes and then to nanotube hydrogels through simple point mutations guided by interfacial interaction redesign. We demonstrate that site 70, which lies in the flexible FG loop of the capsid protein (CP), is a "magic" site that can largely dictate the final morphology of assemblies. By varying the amino acid at site 70, with the aid of a cysteine-to-alanine mutation at site 46, we achieved the assembly of double-helical or single-helical nanotubes in addition to nanocages. Furthermore, an additional cysteine substitution on the surface of nanotubes mediated their cross-linking to form hydrogels with reducing agent responsiveness. The hierarchical self-assembly system allowed for the investigation of morphology-related immunogenicity of MS2 CPs, which revealed dramatic differences among nanocages, nanotubes, and nanotube hydrogels in terms of immune response types, antibody levels and T cell functions. This study provides insights into the assembly manipulation of protein nanomaterials and the customized design of nanovaccines and drug delivery systems.

Furan-based AIE supramolecular self-assembly system for fluorescence detection of Ag+

A novel furan-based Aggregation-Induced Emission (AIE) supramolecular self-assembling gelator (BM) was designed and synthesized, which could self-assemble into a stable supramolecular gel (OBM) in the 1,2-propanediol. OBM demonstrates “turn-off” fluorescence detection of Ag+, with excellent selectivity and a low limit of detection (LOD) of 1.168×10−8 M. The self-assembly process and ion recognition sensing mechanism of OBM were comprehensively investigated by Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray Photoelectron Spectroscopy (XPS), and rheological measurements. More importantly, single crystal were successfully obtained to validate the self-assembly process. This study provides a novel approach to constructing a multifunctional AIE self-assembly system.

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.

Host-Guest Stimuli-Responsive Click Chemistry.

Click chemistry has reached its maturity as the weapon of choice for the irreversible ligation of molecular fragments, with over 20 years of research resulting in the development or improvement of highly efficient kinetically controlled conjugation reactions. Nevertheless, traditional click reactions can be disadvantageous not only in terms of efficiency (side products, slow kinetics, air/water tolerance, etc.), but also because they completely avoid the possibility to reversibly produce and control bound/unbound states. Recently, non-covalent click chemistry has appeared as a more efficient alternative, in particular by using host-guest self-assembled systems of high thermodynamic stability and kinetic lability. This review discusses the implementation of molecular switches in the development of such non-covalent ligation processes, resulting in what we have termed stimuli-responsive click chemistry, in which the bound/unbound constitutional states of the system can be favored by external stimulation, in particular using host-guest complexes. As we exemplify with handpicked selected examples, these supramolecular systems are well suited for the development of human-controlled molecular conjugation, by coupling thermodynamically regulated processes with appropriate temporally resolved extrinsic control mechanisms, thus mimicking nature and advancing our efforts to develop a more function-oriented chemical synthesis.

Study on 2D Molecular Networks of Flexible Pentacarboxylic Acid Ligands Induced by Ether Bonds in Response to Selective Guest Inclusion.

The flexibility of ligands allows for their bending, twisting, or rotation to adopt various conformations, leading to distinct symmetries during the self-assembled process. Flexible aromatic acid ligands modified by ether bonds are a promising type of self-assembled module when it comes to surfaces. Here, two pentacarboxylic acid ligands (H5L1 and H5L2) with minor skeleton differences have successfully self-assembled into disparate porous networks on the graphite surface and demonstrated excellent potential for the inclusion of guest molecules. The H5L1 molecule's network structure only accommodates coronene (COR) molecules. With fewer COR molecules, H5L1 molecules act as a host template to accommodate the COR molecules. When there are too many COR molecules, COR molecules will induce H5L1 molecules to transform into a new host-guest nanostructure. Additionally, H5L2 molecules showed the ability to capture C70 molecules and exhibited cavity selectivity. However, the assembled network of H5L2 was slightly deformed in attempts to trap the COR molecules. To understand these phenomena more deeply, various assembled mechanisms were analyzed in combination with building theoretical models and energy analysis. These results reveal the great potential of flexible aromatic acid ligands in two-dimensional self-assembly and host-guest systems for their application in related fields.

Multiparticle collision dynamics simulations of hydrodynamic interactions in colloidal suspensions: How well does the discrete particle approach do at short range?

The multiparticle collision dynamics (MPCD) simulation method is an attractive technique for studying the effects of hydrodynamic interactions in colloidal suspensions because of its flexibility, computational efficiency, and ease of implementation. Here, we analyze an extension of the basic MPCD method in which colloidal particles are discretized with a surface mesh of sensor nodes/particles that interact with solvent particles (MPCD + Discrete Particle or MPCD + DP). We use several situations that have been described analytically to probe the impact of colloidal particle mesh resolution on the ability of the MPCD + DP method to resolve short-ranged hydrodynamic interactions, which are important in crowded suspensions and especially in self-assembling systems that create high volume fraction phases. Specifically, we consider (A) hard-sphere diffusion near a wall, (B) two-particle diffusion, (C) hard-sphere diffusion in crowded suspensions, and (D) the dynamics of aggregation in an attractive colloidal suspension. We show that in each case, the density of sensor nodes plays a significant role in the accuracy of the simulation and that a surprisingly high number of surface nodes are needed to fully capture hydrodynamic interactions.

Automated H2O2 monitoring during photo-Fenton processes using an Arduino self-assembled automatic system

A cheap and easy to use Arduino self-assembled automatic system was employed to continuously monitor the hydrogen peroxide consumption during the photo-Fenton degradation of caffeine, selected as model target compound. The automatic system made it possible to measure the H2O2 concentration in the reaction cell via a colorimetric reaction and to take samples for HPLC analysis minimising the operator manual intervention and exposure to UV radiation. The obtained results were compared in terms of LOD and LOQ with H2O2 measurements manually performed using UV–Vis spectrophotometry, evidencing better analytical performance when using the automatic system; LOD and LOQ were respectively 0.032 mM and 0.106 mM for the automatic system against 0.064 mM and 0.213 mM for UV–Vis spectrophotometry. Furthermore, the photo-Fenton treatment was optimised by means of a Design of Experiments (DoE) investigating the effect of added H2O2 concentration, iron concentration and caffeine initial concentration on system performances. The use of the automatic device for such monitoring provided several advantages: automation (with consequent reduction of the workload), measurement increased precision, reduced reagents consumption and waste production in agreement with the principles of Green Analytical Chemistry.

Tunable Macroscopic Alignment of Self-Assembling Peptide Nanofibers.

Progress in the design and synthesis of nanostructured self-assembling systems has facilitated the realization of numerous nanoscale geometries, including fibers, ribbons, and sheets. A key challenge has been achieving control across multiple length scales and creating macroscopic structures with nanoscale organization. Here, we present a facile extrusion-based fabrication method to produce anisotropic, nanofibrous hydrogels using self-assembling peptides. The application of shear force coinciding with ion-triggered gelation is used to kinetically trap supramolecular nanofibers into aligned, hierarchical macrostructures. Further, we demonstrate the ability to tune the nanostructure of macroscopic hydrogels through modulating phosphate buffer concentration during peptide self-assembly. In addition, increases in the nanostructural anisotropy of fabricated hydrogels are found to enhance their strength and stiffness under hydrated conditions. To demonstrate their utility as an extracellular matrix-mimetic biomaterial, aligned nanofibrous hydrogels are used to guide directional spreading of multiple cell types, but strikingly, increased matrix alignment is not always correlated with increased cellular alignment. Nanoscale observations reveal differences in cell-matrix interactions between variably aligned scaffolds and implicate the need for mechanical coupling for cells to understand nanofibrous alignment cues. In total, innovations in the supramolecular engineering of self-assembling peptides allow us to decouple nanostructure from macrostructure and generate a gradient of anisotropic nanofibrous hydrogels. We anticipate that control of architecture at multiple length scales will be critical for a variety of applications, including the bottom-up tissue engineering explored here.

A Self-Assembled MOF-Escherichia Coli Hybrid System for Light-Driven Fuels and Valuable Chemicals Synthesis.

The development of semi-artificial photosynthetic systems, which integrate metal-organic frameworks (MOFs) with industrial microbial cell factories for light-driven synthesis of fuels and valuable chemicals, represents a highly promising avenue for both research advancements and practical applications. In this study, an MOF (PCN-222) utilizing racemic-(4-carboxyphenyl) porphyrin and zirconium chloride (ZrCl4) as primary constituents is synthesized. Employing a self-assembly process, a hybrid system is constructed, integrating engineered Escherichia coli (E. coli) to investigate light-driven hydrogen and lysine production. These results demonstrate that the light-irradiated biohybrid system efficiently produce H2 with a quantum efficiency of 0.75% under full spectrum illumination, the elevated intracellular reducing power NADPH is also observed. By optimizing the conditions, the biohybrid system achieves a maximum lysine production of 18.25mg L-1, surpassing that of pure bacteria by 332%. Further investigations into interfacial electron transfer mechanisms reveals that PCN-222 efficiently captures light and facilitates the transfer of photo-generated electrons into E. coli cells. It is proposed that the interfacial energy transfer process is mediated by riboflavin, with facilitation by secreted small organic acids acting as hole scavengers for PCN-222. This study establishes a crucial foundation for future research into the light-driven biomanufacturing using E. coli-based hybrid systems.

Evaluation of layer-by-layer assembly systems for drug delivery and antimicrobial properties in orthopaedic application

Layer-by-layer self-assembly systems were developed using monolayer and multilayer carriers to prevent infections and improve bone regeneration of porous Ti-6Al-4V scaffolds. These polymeric carriers incorporated (Gel/Alg-IGF-1 + Chi-Cef) and (4Gel/Alg-IGF-1 + Chi-Cef) on the surface of porous implants produced via electron beam melting (EBM). The results showed that the drug release from multilayer carriers was higher than that of monolayers after 14 days. However, the carrier containing Gel/Alg-IGF-1 + Chi-Cef exhibited more sustained behavior. Cell morphology was characterized, revealing that multilayer carriers had higher cell adhesion than monolayers. Additionally, cell differentiation was significantly greater for (Gel/Alg-IGF-1) + Chi-Cef, and (4Gel/Alg-IGF-1) + Chi-Cef multilayer carriers than for the monolayer groups after 7 days. Notably, the drug dosage was effective and did not interfere, and the cell viability assay showed safe results. Antibacterial evaluations demonstrated that both multilayer carriers had a greater effect on Staphylococcus aureus during treatment. The carriers containing lower alginate had notably less effect than the other studied carriers. This study aimed to test systems for controlling drug release, which will be applied to improve MG63 cell behavior and prevent bacterial accumulation during orthopaedic applications.

Long-Range Imaging LiDAR with Multiple Denoising Technologies

The ability to capture and record high-resolution images over long distances is essential for a wide range of applications, including connected and autonomous vehicles, defense and security operations, as well as agriculture and mining industries. Here, we demonstrate a self-assembled bistatic long-range imaging LiDAR system. Importantly, to achieve high signal-to-noise ratio (SNR) data, we employed a comprehensive suite of denoising methods including temporal, spatial, spectral, and polarization filtering. With the aid of these denoising technologies, our system has been validated to possess the capability of imaging under various complex usage conditions. In terms of distance performance, the test results achieved ranges of over 4000 m during daylight with clear weather, 19,200 m at night, 6700 m during daylight with haze, and 2000 m during daylight with rain. Additionally, it offers an angular resolution of 0.01 mrad. These findings demonstrate the potential to offer comprehensive construction strategies and operational methodologies to individuals seeking long-range LiDAR data.

Leucine zipper as a bridge for transaminase self-assembly: A fusion enzyme for efficient chiral conversion of d-phenylglycine

Amino acid transferase is a family of enzymes used to catalyze and separate chiral amino acids. However, due to the low efficiency, by-products and reverse reactions occur in cascade reactions. Therefore, in the research, phenylglycine aminotransferase and aspartate aminotransferase were self-assembled in vitro by leucine zipper. The self-assembled enzyme system with d-phenylglycine and α-ketoglutarate as substrates were used for the chiral transformation reaction. By studying the enzyme combination, kinetic reaction stability and catalytic efficiency, it was found that the self-assembled enzyme showed improved stability and better affinity to the substrate than the control and achieved only ee value of 17.86% for the control at the substrate ratio was 1:2. In contrast, the self-assembled enzyme basically catalyzed the complete conversion of d-Phg to l-Phg, with the ee value as 99%. These results demonstrated the feasibility of the leucine zipper and the conversion of d-phenylglycine to the l-type by fusion enzyme.

Phytosomes in herbal formulation: an updated review

Phytosomes, a phospholipid-based self-assembled delivery system, can improve oral bioavailability of polyphenolic compounds. These systems, prepared by reacting polyphenolic phytoconstituents with phospholipid, can enhance the passage of lipophilic herbal constituents across the lipid membrane. Phytosomes are used in various herbal drugs like Ginkgo biloba,Camellia sinensis. Recent advancements in phytosomes technology have led to the development of transdermal routes for delivering phytoconstituents. These products are increasingly used in dietary supplements for homeostatic management of inflammation, toxicities, cancers, and weight loss. This technique increases the hydrophilicity of highly lipophilic drugs, making them suitable for drug delivery and allowing hydrophilic phytoconstituents to cross biological membranes. Researchers are exploring the transdermal route as a potential way to deliver phytoconstituents, which are increasingly being used in dietary supplements for homeostatic management of various diseases. We will explore an updated review of Phytosomes in herbal formulation.

A combinatorial library of two-component gelators based on acid-base complexes of pivalic acid and tert-butylacetic acid

Multi-component self-assembled systems can form highly ordered, complex architectures with diverse morphologies which can be utilized for various high-tech applications. Moreover, a combinatorial library approach can allow us to screen various backbones at the same time for tailoring the functionalities as desired. We report two series of multi-component salt-based gelators based on pivalic acid and tert-butylacetic acid (TBAA) using same set of amines. The two sets of compounds were scrutinized for their gelation performance in a variety of solvents and compared, in order to assess and validate the basic principles behind gelation behavior. The role of acid and effect of increasing a methylene group on the gelation behavior, rheological properties and morphology has been probed.

Scaling up of a Self-Confined Catalytic Hybridization Circuit for Robust microRNA Imaging.

The precise regulation of cellular behaviors within a confined, crowded intracellular environment is highly amenable in diagnostics and therapeutics. While synthetic circuitry system through a concatenated chemical reaction network has rarely been reported to mimic dynamic self-assembly system. Herein, a catalytic self-defined circuit (CSC) for the hierarchically concatenated assembly of DNA domino nanostructures is engineered. By incorporating pre-sealed symmetrical fragments into the preying hairpin reactants, the CSC system allows the hierarchical DNA self-assembly via a microRNA (miRNA)-powered self-sorting catalytic hybridization reaction. With minimal strand complexity, this self-sustainable CSC system streamlined the circuit component and achieved localization-intensified cascaded signal amplification. Profiting from the self-adaptively concatenated hybridization reaction, a reliable and robust method has been achieved for discriminating carcinoma tissues from the corresponding para-carcinoma tissues. The CSC-sustained self-assembly strategy provides a comprehensive and smart toolbox for organizing various hierarchical DNA nanostructures, which may facilitate more insights for clinical diagnosis and therapeutic assessment.