Peptide Amphiphilic Supramolecular Nanogels: Competent Host for Notably Efficient Lipase-Catalyzed Hydrolysis of Water-Insoluble Substrates.

The present work depicts the development of stable nanogels in an aqueous medium that were exploited for efficient surface-active lipase-catalyzed hydrolysis of water-insoluble substrates. Surfactant-coated gel nanoparticles (neutral NG1, anionic NG2, and cationic NG3) were prepared from peptide amphiphilic hydrogelator (G1, G2, and G3, respectively) at different hydrophilic and lipophilic balance (HLB). Chromobacterium viscosum (CV) lipase activity towards hydrolysis of water-insoluble substrates (p-nitrophyenyl-n-alkanoates (C4-C10)) in the presence of nanogels got remarkably improved by ~1.7-8.0 fold in comparison to that in aqueous buffer and other self-aggregates. An increase in hydrophobicity of the substrate led to a notable improvement in lipase activity in the hydrophilic domain (HLB>8.0) of nanogels. The micro-heterogeneous interface of small-sized (10-65 nm) nanogel was found to be an appropriate scaffold for immobilizing surface-active lipase to exhibit superior catalytic efficiency. Concurrently, the flexible conformation of lipase immobilized in nanogels was reflected in its secondary structure having the highest α-helix content from the circular dichroism spectra.

Annealing effects on the magnetic and magnetotransport properties of iron oxide nanoparticles self-assemblies.

In magnetic tunnel junctions based on iron oxide nanoparticles the disorder and the oxidation state of the surface spin as well as the nanoparticles functionalization play a crucial role in the magnetotransport properties. In this work, we report a systematic study of the effects of vacuum annealing on the structural, magnetic and transport properties of self-assembled ∼10 nm Fe3O4nanoparticles. The high temperature treatment (from 573 to 873 K) decomposes the organic coating into amorphous carbon, reducing the electrical resistivity of the assemblies by 4 orders of magnitude. At the same time, the 3.Fe2+/(Fe3++Fe2+) ratio is reduced from 1.11 to 0.13 when the annealing temperature of the sample increases from 573 to 873 K, indicating an important surface oxidation. Although the 2 nm physical gap remains unchanged with the thermal treatment, a monotonous decrease of tunnel barrier width was obtained from the electron transport measurements when the annealing temperature increases, indicating an increment in the number of defects and hot-spots in the gap between the nanoparticles. This is reflected in the reduction of the spin dependent tunneling, which reduces the interparticle magnetoresistance. This work shows new insights about influence of the nanoparticle interfacial composition, as well their the spatial arrangement, on the tunnel transport of self-assemblies, and evidence the importance of optimizing the nanostructure fabrication for increasing the tunneling current without degrading the spin polarized current.

Cationic lipid-conjugated bis-arylidene oxindole derivatives as broad-spectrum breast cancer-selective therapeutics.

Breast cancer is a heterogeneous malignancy with wide-ranging variations in therapeutic responses, overall survival etc. Major challenges for available chemotherapeutic agents in achieving clinical success are in maintaining systemic bio-distribution and avoiding non-specific adverse effects. Bis-arylidene oxindoles are estrogen receptor (ER)-selective bioactive molecules with moderate potency. In here, we have designed, synthesized and evaluated a series of twin aliphatic chain cationic lipid-conjugated bis-arylidene oxindole molecules with variations in nature of linker, lengths of carbon spacer and hydrophobic twin chains. We observed that among the various structural analogues, C8 twin-chain containing molecules, PGC8, S2C8 and S3C8 showed effective cancer cell-selective cytotoxicity in different cancer cell lines with an IC50 ranging from 4 to 7 µM. These molecules selectively induced apoptosis, ROS production and cell cycle inhibition at G1/S phase in ER + breast cancer cells but not in non-cancer cells. Additionally, these molecules formed homogenous self-assemblies exhibiting effective hydrodynamic diameter with positive surface charge. The self-assemblies also showed prominent cancer cell-selective uptake and DNA-binding abilities. Hence, we have shown successful incorporation of dexamethasone to the self-assemblies, and its enhanced cytotoxicity even in ER-negative breast cancer cells. All these results indicate that PGC8, S2C8 and S3C8 molecules, albeit their potent and selective ER-positive anti-breast cancer activity, can be repurposed as targeted delivery systems and hold promise as unique, broader spectrum breast cancer cell-selective therapeutic payloads.

Recent Advances in Functional Nanomaterials for Diagnostic and Sensing Using Self-Assembled Monolayers.

Functional nanomaterials have attracted attention by producing different structures in any field. These materials have several potential applications, including medicine, electronics, and energy, which provide many unique properties. These nanostructures can be synthesized using various methods, including self-assembly, which can be used for the same applications. This unique nanomaterial is increasingly being used for biological detection due to its unique optical, electrical, and mechanical properties, which provide sensitive and specific sensors for detecting biomolecules such as DNA, RNA, and proteins. This review highlights recent advances in the field and discusses the fabrication and characterization of the corresponding materials, which can be further applied in optical, magnetic, electronic, and sensor fields.

Controlled Self-assembly of Gold(I) Complexes by Multiple Kinetic Aggregation States with Nonlinear Optical and Waveguide Properties.

Introduction of multiple kinetic aggregation states (Aggs) into the self-assembly pathway could bring complexity and flexibility to the self-assemblies, which is difficult to realize due to the delicate equilibria established among different Aggs bonded by weak noncovalent interactions. Here, we describe a series of chiral and achiral d10 AuI bis(N-heterocyclic carbene, NHC) complexes, and the achiral complex could undergo self-assembly with multiple kinetic Aggs. Generation of multiple kinetic Aggs was realized by applying chiral or achiral seeds exhibiting large differences in elongation temperatures for their respective cooperative self-assembly processes. We further showed that the chiral AuI self-assemblies having non-centrosymmetric packing forms exhibit nonlinear optical response of second harmonic generation (SHG), while the SHG signal is absent in the achiral analogue. The crystalline achiral AuI self-assemblies could function as optical waveguides with strong emission polarization.

Metal-Ligand Interactions and Oligo(p-phenylene vinylene) Derivatives Based Supramolecular Polymer Possessing Variable Fluorescence Colors.

Fluorescent supramolecular polymers combine the benefits of supramolecular polymers in terms of dynamic nature with the optoelectronic features of incorporated fluorophores. However, the majority of fluorescent supramolecular polymers can only exhibit a single fluorescent state, restricting their applications. Incorporating J-type dyes into supramolecular monomers is expected to impart supramolecular polymers with variable fluorescence colors, because the aggregation mode of J-type dyes is closely related to the formation of supramolecular polymers. Herein, the authors report a supramolecular polymer [M1·Zn(OTf)2 ]n , in which the monomer M1 contains a J-type dye, oligo(p-phenylene vinylene) derivative, and two terpyridine ends. The M1 + Zn(OTf)2 solutions exhibit fluorescence color changes varying from cyan to yellow-green in the monomer concentration ranging from 0.04 to 1.00 mm. Moreover, based on the outputs from laser scanning confocal microscopy, the fluorescence color transition during the formation of supramolecular polymers is intuitively proven. Additionally, considering the close relationship between the supramolecular polymer structure and the fluorescence color, the fluorescence color can be regulated by introducing tetraethylammonium hydroxide that can bind with Zn2+ competitively to break up the structure of the supramolecular polymer.

Stimuli-Responsive Pickering Emulsions Regulated via Polymerization-Induced Self-Assembly Nanoparticles.

With the development of reversible deactivated radical polymerization techniques, polymerization-induced self-assembly (PISA) is emerging as a facile method to prepare block copolymer nanoparticles in situ with high concentrations, providing wide potential applications in different fields, including nanomedicine, coatings, nanomanufacture, and Pickering emulsions. Polymeric emulsifiers synthesized by PISA have many advantages comparing with conventional nanoparticle emulsifiers. The morphologies, size, and amphiphilicity can be readily regulated via the synthetic process, post-modification, and external stimuli. By introducing stimulus responsiveness into PISA nanoparticles, Pickering emulsions stabilized with these nanoparticles can be endowed with "smart" behaviors. The emulsions can be regulated in reversible emulsification and demulsification. In this review, the authors focus on recent progress on Pickering emulsions stabilized by PISA nanoparticles with stimuli-responsiveness. The factors affecting the stability of emulsions during emulsification and demulsification are discussed in details. Furthermore, some viewpoints for preparing stimuli-responsive emulsions and their applications in antibacterial agents, diphase reaction platforms, and multi-emulsions are discussed as well. Finally, the future developments and applications of stimuli-responsive Pickering emulsions stabilized by PISA nanoparticles are highlighted.

Shaping Block Copolymer Microparticles by Positively Charged Polymeric Nanoparticles.

Shape-transforming block copolymer (BCP) microparticles have attracted extensive attention due to their promising applications in nanotechnology, biomedicines, interfacial science, and other fields. As their performance is highly associated to their shape and structure, it is very important to realize the precise control of particle shape. In this report, a method is proposed to regulate the shape and structure of polystyrene-b-polydimethoxysiloxane (PS-b-PDMS) microparticles by using positively charged core-crosslinked nanoparticles (CNPs) as a cosurfactant, combining with cationic surfactant cetyltrimethylammonium bromide (CTAB). The electrostatic repulsive interactions between CNPs and CTAB dominate the shape of PS-b-PDMS particles. Upon introducing NaCl, the electrostatic repulsion is reduced, resulting in the reshape of PS-b-PDMS particles from striped Janus ellipsoids to onion-like microspheres at a critical concentration of NaCl (cNaCl ). Interestingly, it is found that the critical cNaCl first increases then reaches a plateau, with the increase in the crosslinking degree of the CNPs. The work provides a simple strategy to tailor the morphology of BCPs by manipulating the electrostatic interaction.

Interfacial Self-Assembly of Amphiphilic Core-Shell Bottlebrush Block Copolymers Toward Responsive Photonic Balls Bearing Ionic Channels.

Photonic balls can be facilely obtained through interfacial self-assembly of amphiphilic bottlebrush block polymers (BBCPs) within a water-in-oil-in-water (w/o/w) multiple emulsion system, and polystyrene (PS) has been employed as the skeleton of the balls showing no responsive properties. Here, the design and synthesis of core-shell BBCPs are demonstrated with a poly(tert-butyl acrylate)-block-polystyrene (PtBA-b-PS) block copolymer as the hydrophobic side chains and poly(ethylene glycol) as the hydrophilic block. Interfacial self-assembly of the core-shell BBCPs within shrinking droplets produces porous microspheres with full-spectrum structural colors through an organized spontaneous emulsification process. The PtBA core wrapped by PS in the skeleton of the balls can be converted into polyacrylic acid (PAA) forming an ionic channel responsive to pH variations. Consequently, the hydrolyzed photonic balls show different colors under different pH conditions dependent on varying degrees of ionization and hydration of the PAA channel. Reflected colors can be verified using an optical spectrometer, providing an effective strategy for precise pH indication.

Enantioselective Tail-to-Head Terpene Cyclizations by Optically Active Hexameric Resorcin[4]arene Capsule Derivatives.

Molecular capsules enable the conversion of substrates inside a closed cavity, mimicking to some extent enzymatic catalysis. Chirality transfer from the molecular capsule onto the encapsulated substrate has been only studied in a few cases. Here we demonstrate that chirality transfer is possible inside a rather large molecular container of approximately 1400 Å3 . Specifically, we present 1) the first examples of optically active hexameric resorcin[4]arene capsules, 2) their ability to enantioselectively catalyze tail-to-head terpene cyclizations, and 3) the surprisingly high sensitivity of enantioselectivity on the structural modifications.

Structural Transformation of Surface-Confined Porphyrin Networks by Addition of Co Atoms.

The self-assembly of a nickel-porphyrin derivative (Ni-DPPyP) containing two pyridyl coordinating sites and two pentyl chains at trans meso positions was studied with scanning tunneling microscopy (STM), X-ray photoelectron spectroscopy (XPS) and low energy electron diffraction (LEED) on Au(111). Deposition of Ni-DPPyP onto Au(111) gave rise to a close-packed network for coverages smaller or equal to one monolayer as revealed by STM and LEED. The molecular arrangement of this two-dimensional network is stabilized via hydrogen bonds formed between the pyridyl's nitrogen and hydrogen atoms from the pyrrole groups of neighboring molecules. Subsequent deposition of cobalt atoms onto the close-packed network and post-deposition annealing at 423 K led to the formation of a Co-coordinated hexagonal porous network. As confirmed by XPS measurements, the porous network is stabilized by metal-ligand interactions between one cobalt atom and three pyridyl ligands, each pyridyl ligand coming from a different Ni-DPPyP molecule.

Nanomedicine to target multidrug resistant tumors.

Nanomedicine employs nanotechnologies to develop innovative applications, and more specifically nano-objects in the field of human health, through exploitation of the physical, chemical and biological properties of materials at the nanoscale. The use of nanovehicles capable of transporting and releasing the active therapeutic payload into target cells, particularly in the case of cancer or inflammatory diseases, can also enhance diagnosis. Therefore, nanomedicines improve the benefit/risk ratio of drugs by increasing their bioavailability, selectivity, and efficacy in the target tissue, while reducing the necessary doses and hence diminishing untoward toxicity to healthy tissues. Overcoming multidrug resistance (MDR) to antitumor agents is a central goal of cancer research and therapeutics, making it possible to treat these diseases more accurately and effectively. The adaptability of nanomedicines e.g. modulation of their components, surface functionalization, encapsulation of various active therapeutics as well as the possibility of combining several treatments using a single nanoparticle platform, are characteristics which are perfectly poised to address classical chemoresistance, a major obstacle towards curative cancer therapy. In this review, we discuss an assortment of nanomedicines along with those that should be developed in order to surmount cancer MDR; these include exosomes, natural compounds, lipid nanocapsules, prodrug self-assemblies, and gold nanoparticles.

Peptide-Assisted Nucleic Acid Delivery Systems on the Rise.

Concerns associated with nanocarriers' therapeutic efficacy and side effects have led to the development of strategies to advance them into targeted and responsive delivery systems. Owing to their bioactivity and biocompatibility, peptides play a key role in these strategies and, thus, have been extensively studied in nanomedicine. Peptide-based nanocarriers, in particular, have burgeoned with advances in purely peptidic structures and in combinations of peptides, both native and modified, with polymers, lipids, and inorganic nanoparticles. In this review, we summarize advances on peptides promoting gene delivery systems. The efficacy of nucleic acid therapies largely depends on cell internalization and the delivery to subcellular organelles. Hence, the review focuses on nanocarriers where peptides are pivotal in ferrying nucleic acids to their site of action, with a special emphasis on peptides that assist anionic, water-soluble nucleic acids in crossing the membrane barriers they encounter on their way to efficient function. In a second part, we address how peptides advance nanoassembly delivery tools, such that they navigate delivery barriers and release their nucleic acid cargo at specific sites in a controlled fashion.

Investigation of Morphology-Controlled Ultrafast Relaxation Processes of Aggregated Porphyrin.

Here, we have synthesized rod and flake shaped morphology of porphyrin aggregates from 5, 10, 15, 20-tetra (4-n-octyloxyphenyl) porphyrin (4-opTPP) molecule which are evident from scanning electron microscopy (SEM). The formation of J-type aggregation is evident from steady state and time-resolved fluorescence spectroscopic studies. Ultrafast transient absorption spectroscopic studies reveal that the excited state lifetime is controlled by the morphology and the time constant for S1→S0 relaxation changes from 3.05 ps to 744 ps with changing the shape from rod to flake, respectively. In spite of similar exciton coupling energy in both the aggregates, the flake shaped aggregates undergo a faster exciton relaxation process and the non-radiative relaxation channels are found to depend on the shape of aggregates. The fundamental understanding of morphology controlled ultrafast relaxation processes of aggregated porphyrin is important for designing efficient light harvesting devices.

Cylindrical Zwitterionic Particles via Interpolyelectrolyte Complexation on Molecular Polymer Brushes.

The fabrication of macromolecular architectures with high aspect ratio and well-defined internal and external morphologies remains a challenge. The combination of template chemistry and self-assembly concepts to construct peculiar polymer architectures via a bottom-up approach is an emerging approach. In this study, a cylindrical template-namely a core-shell molecular polymer brush-and linear diblock copolymers (DBCP) associate to produce high aspect ratio polymer particles via interpolyelectrolyte complexation. Induced, morphological changes are studied using cryogenic transmission electron and atomic force microscopy, while the complexation is further followed by isothermal titration calorimetry and ξ-potential measurements. Depending on the nature of the complexing DBCP, distinct morphological differences can be achieved. While polymers with a non-ionic block lead to internal compartmentalization, polymers featuring zwitterionic domains lead to a wrapping of the brush template.

Supramolecular Recognition-Mediated Layer-by-Layer Self-Assembled Gold Nanoparticles for Customized Sensitivity in Paper-Based Strip Nanobiosensors.

Herein, a smart supramolecular self-assembly-mediated signal amplification strategy is developed on a paper-based nanobiosensor to achieve the sensitive and customized detection of biomarkers. The host-guest recognition between ß-cyclodextrin-coated gold nanoparticles (AuNPs) and 1-adamantane acetic acid or tetrakis(4-carboxyphenyl)porphyrin is designed and applied to the layer-by-layer self-assembly of AuNPs at the test area of the strip. Thus, the amplified platform exhibits a high sensitivity with a detection limit at subattogram levels (approximately dozens of molecules per strip) and a wide dynamic range of concentration over seven orders of magnitude. The applicability and universality of this sensitive platform are demonstrated in clinically significant ranges to measure carcinoembryonic antigen and HIV-1 capsid p24 antigen in spiked serum and clinical samples. The customized biomarker detection ability for the on-demand needs of clinicians is further verified through cycle incubation-mediated controllable self-assembly. Collectively, the supramolecular self-assembly amplification method is suitable as a universal point-of-care diagnostic tool and can be readily adapted as a platform technology for the sensitive assay of many different target analytes.

Morphology-tunable and pH-responsive supramolecular self-assemblies based on AB2-type host-guest-conjugated amphiphilic molecules for controlled drug delivery.

Although stimuli-responsive supramolecular self-assemblies have been constructed, the controlled drug delivery induced by morphology transitions of these supramolecular self-assemblies on the basis of host-guest-conjugated monomers (HGCMs) are few reported. In this paper, the self-assembly behaviors of AB2-type HGCMs, e.g., ß-cyclodextrin-benzimidazole2 (ß-CD-BM2), were investigated at neutral and acidic pH conditions, respectively. Specifically, ß-CD-BM2 first self-assembled into fan-shaped supramolecular self-assemblies with a hydrodynamic diameter of 163 nm at neutral pH, whereas they were further dissociated into spherical supramolecular self-assemblies with a size of 52 nm under acidic conditions. This morphology transition process was utilized to conduct a two-stage DOX delivery under neutral and acidic pH. Basic cell experiments demonstrated that the drug-loaded ß-CD-BM2-based supramolecular self-assemblies with varied morphology could inhibit cancer cell proliferation, indicating their potential application in the field of drug delivery.

Semi-Fluorinated Methacrylates: A Class of Versatile Monomers for Polymerization-Induced Self-Assembly.

A series of polymerization-induced self-assembly (PISA) formulations are developed based on reversible addition-fragmentation chain-transfer (RAFT) dispersion polymerization of semi-fluorinated methacrylates. Alcoholic RAFT dispersion polymerization of 2-(perfluorobutyl)ethyl methacrylate (FBEMA), 2-(perfluorohexyl)ethyl methacrylate (FHEMA), and 2-(perfluorooctyl)ethyl methacrylate (FOEMA) is systematically evaluated to extend the general usability of semi-fluorinated methacrylates to PISA. The nanostructure of the assemblies is correlated to the side-chain length of the monomer: RAFT dispersion polymerization of FBEMA produces spherical micelles, wormlike micelles, and vesicles depending on its degree of polymerization (DP), while only spheres are generated for the PISA of FHEMA. PISA of FOEMA generates liquid crystalline cylindrical micelles, whose diameter increases with the DP of FOEMA. These results demonstrate the general feasibility of semi-fluorinated methacrylates to PISA. Besides, PISA of FHEMA is also realized in a variety of solvents, including iso-propanol, toluene, dioxane, and dimethyl formamide, exhibiting the superior solvent serviceability of the PISA formulations based on semi-fluorinated methacrylates.

Adjuvants Based on Synthetic Mycobacterial Cord Factor Analogues: Biophysical Properties of Neat Glycolipids and Nanoself-Assemblies with DDA.

Synthetic mycobacterial cord factor analogues, e.g., trehalose 6,6'-dibehenate (TDB), are highly promising adjuvants due to their strong immunopotentiating capabilities, but their biophysical properties have remained poorly characterized. Here, we report the synthesis of an array of synthetic TDB analogues varying in acyl chain length, degree of acylation, and headgroup display, which was subjected to biophysical characterization of neat nondispersed self-assembled nanostructures in excess buffer and as aqueous dispersions with cationic dimethyldioctadecylammonium (DDA) bromide. The array comprised trehalose mono- (TMX) and diester (TDX) analogues with symmetrically shortened acyl chains [denoted by X: arachidate (A), stearate (S), palmitate (P), myristate (Myr), and laurate (L)] and an analogue with a short hydrophilic polyethylene glycol (PEG) linker inserted between the trehalose headgroup of TDS and the acyl chains (PEG-TDS). All dispersions were liposomes, but in contrast to the colloidally stable and highly cationic TDX-containing liposomes, the zeta-potential was significantly reduced for DDA/TMX and DDA/PEG-TDS liposomes, suggesting a charge-shielding effect, which compromises the colloidal stability. An increased d-spacing was observed for the lamellar phase of neat TDB analogues in excess buffer (TDS < TMS < PEG-TDS), confirming that the charge shielding is caused by an extended molecular configuration of the more flexible headgroup. Differential scanning calorimetry showed highly cooperative phase transitions for all tested dispersions albeit the monoesters destabilized the lipid bilayers. Langmuir experiments demonstrated that incorporation of TDXs and PEG-TDS stabilized DDA monolayers due to improved hydrogen bonding and reduced intermolecular repulsions. In conclusion, data suggest that the DDA/TDS dispersions exhibit favorable physicochemical properties rendering these DDA/TDS liposomes an attractive vaccine adjuvant, and they emphasize that not only the receptor binding and immune activation but also the biophysical properties of immunopotentiator formulations should be collectively considered when designing adjuvants with optimal safety, efficacy, and storage stability.

Self-Assembly of Amphiphilic Anthracene-Functionalized ß-Cyclodextrin (CD-AN) through Multi-Micelle Aggregation.

Multi-micelle aggregation (MMA) mechanism is widely acknowledged to explicate large spherical micelles self-assembly, but the process of MMA during self-assembly is hard to observe. Herein, a novel kind of strong, regular microspheres fabricated from self-assembly of amphiphilic anthracene-functionalized ß-cyclodextrin (CD-AN) via Cu(I)-catalyzed azide-alkyne click reactions is reported. The obtained CD-AN amphiphiles can self-assemble in water from primary core-shell micelles to secondary aggregates with the diameter changing from several tens nm to around 600-700 nm via MMA process according to the images of scanning electron microscopy, transmission electron microscopy, and atomic force microscopy as well as the dynamic light scattering measurements, followed by further crosslinking through photo-dimerization of anthracene. What merits special attention is that such photo-crosslinked self-assemblies are able to disaggregate reversibly into primary nanoparticles when changing the solution conditions, which is benefited from the designed regular structure of CD-AN and the rigid ranging of anthracene during assembly, thus confirming the process of MMA.