Electrostatic Self‐Assembly as Route to Supramolecular Structures

We introduce and discuss the recently developed concept of electrostatic self‐assembly for the formation of nanoscale assemblies in solution. As opposed to many approaches to self‐assembly relying on amphiphilicity, the driving force here is electrostatics plus secondary interaction such as stacking of aromatic molecule parts: Polyelectrolyte dendrimers can be linked with multiply charged aromatic dye molecules as “structural counterions” yielding 100 nm scale aggregates of narrow size distribution and different shapes. We discuss competing interaction forces and the potential of this approach to lead to versatile and functional supramolecular structures.

     

Structure Tuning of Electrostatically Self‐Assembled Nanoparticles through pH: The Role of Charge Ratio

Systems that can be controlled through external triggers are of interest for a variety of applications from medicine to energy conversion. Here, the effects of pH on the electrostatic self‐assembly of generation four poly(amidoamine) dendrimers and a divalent azo dye, keeping constant the charge ratio, are discussed. Nanoparticles stabilized by an excess of dendrimer charge form at 3.5 ≤ pH ≤ 8.5. The nanoparticle structure strongly depends on pH: at 7 ≤ pH ≤ 8.5, where only the dendrimer primary amines are protonated, spherical particles form, while at 3.5 ≤ pH < 7 where also the tertiary amines are protonated, cylinders form. Not only the nanoparticle structure but also the interaction of the molecular building blocks is controlled by pH: the dye stacking changes and the twist angle of the dye molecules increases as the pH decreases. Results are related to changes in the dye–dendrimer and dye–dye interaction, in particular spherical nanoparticles are formed when the interaction is small. Finally, the structures at different pH and constant charge ratio are compared to results at constant loading ratio to understand the overall role of the pH in electrostatic self‐assembly. A pH‐responsive shape is of great interest, for example, for drug delivery.     

Hierarchical Self‐Assembly of Peptides and its Applications in Bionanotechnology

Self‐assembled structures obtained from organic molecules have shown great potential for applications in a wide range of domains. In this context, short peptides prove to be a particularly versatile class of organic building blocks for self‐assembled materials. These species afford the biocompatibility and polymorphic richness typical of proteins while allowing synthetic availability and robustness typical of smaller molecules. At the nano‐to‐mesoscale, the architectures obtained from peptide units exhibit stability and a large variety of morphologies, the most common of which are nanotubes, nanoribbons, and nanowires. This review describes the formation of peptide‐based self‐assembled structures triggered by different stimuli (e.g., ionic strength, pH, and polarity), and the interactions that drive the assembling processes. It is surveyed how judicious molecular design is exploited to impart favourable assembling properties to afford systems with desired characteristics. A large body of literature provides the experimental and in silico data to predict self‐assembly in a given peptide system and obtain different supramolecular organizations for applications in a wide range of fields, from transport to sensing, from catalysis to drug delivery and tissue regeneration.     

Self‐Assembly of Globular‐Protein‐Containing Block Copolymers

Self‐assembly has emerged as a powerful approach to control nanostructure in materials containing globular proteins, both through templated self‐assembly and direct self‐assembly of globular protein‐polymer conjugates or fusion proteins. The folded structures of globular proteins that are critical to their function introduce complex shapes and interactions into block copolymers that significantly alter the physics of self‐assembly. This article discusses the different methods for controlling the nanostructure of globular proteins using block copolymers, highlighting efforts at understanding the physics of self‐assembly in concentrated solution and solid‐state bioconjugate copolymers.

     

Light‐Switchable Supramolecular Self‐Assembly of Soft Colloids

Self‐assembly is an efficient strategy of constructing microgel‐based intelligent materials. However, it remains a challenge to realize the reversible self‐assembly of microgels. Herein, a method to guide the self‐assembly of soft colloids with light‐stimuli is proposed, utilizing the light‐responsive host–guest interaction between an azobenzene functionalized nanogel (the guest colloid) and an α‐cyclodextrin functionalized microgel (the host colloid). The two colloids can form a stable colloid cluster when the surface of the host colloid is fully packed with the guest colloids. The colloid cluster can disassemble when irradiated with UV light and reassemble when irradiated with visible light. The reversible colloidal self‐assembly can be controlled by the interplay between the supramolecular and covalent crosslinking, and can also be adjusted by the addition of competitive host molecules. Besides the light‐sensitivity, the colloid cluster inherits the deformability and temperature‐sensitivity from its parent colloids. These features are different from the supramolecular self‐assembly of hard colloids or macroscopic gels, and manifest the as‐prepared colloid cluster potential building blocks of light‐responsive materials.     

Preparation of PEGylated Iodine‐Loaded Nanoparticles via Polymer‐Directed Self‐Assembly

The preparation of size‐tunable PEGylated, iodine‐loaded nanoparticles is investigated for biomedical applications. Di‐iodination of polyvinyl phenol and encapsulation of the iodinated polymer via directed self‐assembly with an amphiphilic polyethylene glycol‐based diblock copolymer are reported. Nanoparticles with iodine loadings up to 45 wt% are achieved using a rapid, scalable process. The size of the nanoparticles can be readily tuned between 35 and 130 nm by increasing the ionic strength of the antisolvent used during nanoparticle self‐assembly. The resulting PEGylated iodine‐loaded nanoparticles have potential applications in nanomedicine for 1) quantitative biodistribution analysis via inductively coupled plasma mass spectrometry (ICP‐MS) or 2) X‐ray contrast in biomedical imaging. For quantitative biodistribution studies using ICP‐MS, a limit of detection of 2 µg mL^?1 in mouse serum is achieved. For biomedical imaging, the X‐ray attenuation rates are comparable to currently commercially available iodine‐based contrast agents. Therefore, encapsulation of the iodinated polymer enables formulation of trackable, size tunable nanoparticles as a versatile platform for developing nanomedicines.     

The Self‐Assembly of Hydroxypropylcellulose and Carboxyl‐Ended Surfactants to Multi‐Morphological Nanoparticles

Summary: The self‐assembly of HPC and carboxyl‐ended surfactants such as Deac was studied in the present paper. Nanoparticles with multi‐morphologies were fabricated from HPC and Deac, and their diameter and morphology can be controlled by adjusting the molar ratio of glucose units and Deac and the environmental pH value. We also demonstrated the ubiquity of fabricating multi‐morphological nanoparticles from HPC and other carboxyl‐ended surfactants by substituting PDFOA for Deac, and it was confirmed by DLS characterization that nanoparticles with multi‐morphologies were formed at pH = 0.1. Thus the proposed approach shows a considerable potential to fabricate polysaccharide‐based multi‐morphological nanoparticles from water‐soluble polysaccharides and carboxyl‐ended surfactants.

A schematic illustration of the self‐assembly of HPC and Deac to multi‐morphological nanoparticles.     

Size‐Dependent Self‐Assembly of Anisotropic Silica‐Coated Hybrid Nanoparticles

The self‐organization of colloids into defined structures offers the possibility to develop novel materials with exciting properties. However, this requires the understanding and application of the forces governing interparticle association. A novel approach for a size‐dependent anisotropic assembly between nanoparticles is achieved. Janus‐like iron oxide/polystyrene hybrid nanocolloids are prepared by heterophase polymerization and selectively coated with silica on the iron oxide face to gradually form a cavity. Hence, a shallow surface around the hydrophobic polymer face is created, enabling smaller particles of the same nature to be locked by shape complementarity and colloidal steric stabilization. Further coating with silica fixes these assemblies and allows quantitative analysis of the interaction on a nanoscale.

     

PEG and Cholesterol‐Containing Pyromellitates: Synthesis and Self‐Assembly

A new synthetic route for two different amphiphilic macromolecular structures containing hydrophilic poly(ethylene glycol) (PEG) and lipophilic cholesterol fragments is described. The novelty of the synthesis is in combining hydrophilic and lipophilic fragments in a backbone using functional groups of the pyromellitic dianhydride (PMDA) molecule. The ability of the new oligomers to undergo self‐assembly and solubilization of lipophilic molecules in an aqueous medium is compared. The new oligomers form self‐assemblies capable of solubilizing lipophilic “guest” molecules in an aqueous medium. Their high solubilization capacity and biodegradability, as well as other properties (size distribution, ζ‐potential), make the synthesized macromolecules good candidates for biomedical applications. Using the developed approach, amphiphilic macromolecules with regulated surface activity can be synthesized by combining PEG of varying lengths with different hydrophobic fragments (for example, fatty alcohols) in the backbone.

     

Alpha‐Helix Self‐Assembly of Oligopeptides Originated From Beta‐Sheet Keratin

The structure and characterization of the oligopeptide crystals formed from the feather keratin solution obtained by superheated water treatment are reported. The FTIR spectra and ¹H and ¹³C solid‐state NMR results indicate that the peptides, arranged mostly in a beta‐sheet structure in feather, reorganize into a mainly alpha‐helix and less beta‐sheet mixed secondary structure, when self‐assemble from the solution at room temperature. MALDI‐ToF‐ToF spectra confirm that the most primary sequence with the mass 1884 come from the feather keratin 4, KRFA_CHICK of Gallus gallus. The largely preservation of all but cystine amino acid species and the increase of hydrophobic amino acids content in the oligopeptide crystals are proved by the amino acid analysis.     

Self‐Assembly of Nanoparticles in 2D and 3D: Recent Advances and Future Trends

For more than a century, it has been known that emulsions consisting of two immiscible liquids can be rendered from coalescence by means of solid particles, coined as Pickering emulsions. Based on this discovery, novel materials as a result of the formation of 2D and 3D assemblies of nanostructures at liquid–liquid interfaces have been synthesized. These materials have received considerable attention due to several unique attributes of the nanoscale materials within these assemblies and their utilization in a wide arena of niche applications. With the progressive advent of the synthetic strategies of the nanostructures, these assemblies can be engendered to create membranes and capsules with high mechanical strength and desirable porosity and even can be made stimuli‐responsive. The nanostructures, ranging from inorganic particles to proteins to polymeric architectures, possess their stabilizing effects due to excess attachment energies and lead to the maneuvering of exciting structural design, such as colloidosomes and yeastosomes. The ability of the different kind of particles at the nanoscale dimension to self‐assemble at the liquid–liquid interface into ordered superstructures has substantial potential toward the design of exotic electronic, catalytic, optical, magnetic, and biomimetic materials.     

Redox Polymer–Based Nano‐Objects via Polymerization‐Induced Self‐Assembly

Poly(2,2,6,6‐tetramethylpiperidinyloxy‐4‐yl‐methacrylate) (PTMA) redox polymer–based nano‐objects are synthesized by polymerization‐induced self‐assembly with poly[oligo(ethylene glycol) methyl ether methacrylate] and poly[(4‐methacryloyloxy)‐2,2,6,6‐tetramethylpiperidinium chloride] as hydrophilic macro‐chain transfer agents. These hydrophilic blocks are used in order to stabilize hydrophobic PTMA blocks in aqueous medium. The accordingly obtained spherical nano‐objects are observed via transmission electron microscopy analysis. Cyclic voltammetry measurements indicate that the nature and the length of coronal blocks influence the redox process of the PTMA core blocks. Moreover, these electroactive nano‐objects display low viscosities with a shear‐thinning behavior, making them suitable as cathode‐active materials for aqueous flow‐assisted electrochemical systems.     

Temperature‐Triggered Nanosphere Formation Through Self‐Assembly of Amphiphilic Polyphosphazene

Summary: An amphiphilic graft polyphosphazene with a molar ratio of poly(N‐isopropylacrylamide) (PNIPAm) to ethyl glycinate (GlyEt) of 0.54:1 was synthesized. This copolymer in aqueous solution exhibited two temperature induced phase transitions at 17.2 and 33.7 °C, which correspond to the transformation of primary aggregate morphology (at T_ph1) and the collapse of PNIPAm chains (at T_ph2) respectively. Network micelles were assembled in water at lower temperature (far below T_ph1), and then narrowly dispersed nanoparticles were formed above T_ph1, while inter‐nanoparticle aggregation occurred due to the collapse of PNIPAm chains surrounding the GlyEt core when the temperature was above T_ph2. Through solubilization of the hydrophobic drug ibuprofen into polymeric aggregates at lower temperature, drug loaded nanospheres were prepared successfully. In vitro release revealed that sustained drug release was achieved with this novel delivery system. These results suggest that this novel copolymer could be used as a potential drug carrier, especially for the delivery of hydrophobic biocompounds through parenteral administration.

Schematic illustration of the temperature‐triggered self‐assembly process of PNIPAm/GlyEt‐PPP in aqueous solution.     

A Novel Polyelectrolyte with Branched Azo Side Chains: Synthesis,Characterization and Self‐Assembled Nanostructures

A novel polyelectrolyte (PEAPB₆P‐AA) functionalized with branched azo side chains has been synthesized. Aggregation of the azo chromophores of PEAPB₆P‐AA in H₂O/tetrahydrofuran (THF) mixed solvent was detected from its influences on UV‐vis spectra and photoresponsive behavior. Micelle‐like nanoparticles were found when the concentration of PEAPB₆P‐AA increased to above 0.2 mmol·L^–1 in the mixed solvent (THF/H₂O = 1 : 20 vol.‐%). Multilayers of the micelle‐like nanoparticles and poly(diallyldimethylammonium chloride) (PDAC) were fabricated by an electrostatic layer‐by‐layer self‐assembly process. Particularly high wettability of the multilayer surfaces was observed, which affirmed the self‐assembled micelle‐like structure of the particles.     

Double Hydrophilic Block Copolymer Self‐Assembly in Aqueous Solution

Self‐assembly of double hydrophilic block copolymers (DHBCs) in water is an emerging area of research. The self‐assembly process can be derived from aqueous two‐phase systems that are composed of hydrophilic homopolymers at elevated concentration. Consecutively, DHBCs form self‐assembled structures like micelles, vesicles, or particles at high concentrations in water and without the use of external triggers that would change solubility of individual blocks. Careful choice of the two hydrophilic blocks and design of the polymer structure allows formation of self‐assembled structures with high efficiency. The present contribution highlights recent research in the area of DHBC self‐assembly, including the polymer types employed and strategies for crosslinking of the self‐assembled structures. Moreover, an overview of aqueous multiphase systems and theoretical considerations of DHBC self‐assembly are presented, as well as an outlook regarding potential future applications in areas such as the biomedical field.     

Spontaneous Self‐Assembly and Micellization of Random Copolymers in Organic Solvents

Spontaneous self‐assembly of random and statistical copolymers in solution, especially in organic solvents, is unusual due to the structural irregularity of the copolymer chain and close proximity of short incompatible segments. This study describes the first observation of supramolecular structures such as micelles and vesicles formed by a random copolymer in organic solvents. Upon dissolution in methanol or tetrahydrofuran, the random copolymer poly(trifluoroethyl methacrylate‐random‐methacrylic acid) forms small spherical micelles, worm‐like assemblies, and large vesicles spontaneously. Self‐assembly is driven by the high incompatibility between the fluorinated and acidic repeat units. Micelle size can also be altered by the addition of metal ions, which interact with the carboxylic acid groups of methacrylic acid through complexation or Coulombic forces. These findings demonstrate an easy, single‐step approach to creating nanoscale structures with tunable size and morphologies in organic solvents from easily synthesized random copolymers, with potential applications in coatings, selective membranes, catalysis, and drug delivery.     

Synthesis and Self‐Assembly of Functionalized Cyclooctene Block Copolymers via ROMP

A novel block copolymer consisted of MACIT and HCO segments was synthesized via ROMP in the ionic liquid [bmim][PF₆] with good control over the polymerization process. The molecular weight of the block copolymer was estimated by ¹H NMR, and the molar composition ratio of repeating units in the MACIT block to those in the HCO block was 100:120 (120:120 in feed). The micellar characterization was carried out by DLS, AFM, and TEM. The hydrodynamic diameter of the micelles, measured by DLS, was 129 ± 0.09 nm with a narrow distribution (PDI = 0.034). The TEM image showed spherical micelles.

     

Temperature and pH Controlled Self‐Assembly of a Protein–Polymer Biohybrid

A novel pH and temperature dual‐responsive bioconjugate is prepared by grafting thermoresponsive polymer chains from a pH‐responsive protein amelogenin via atom transfer radical polymerization. To the best of our knowledge, this is the first time that amelogenin is exploited to prepare a hybrid biomaterial with new stimuli‐responsive property. In both basic and acidic solutions the protein–polymer bioconjugate is able to self‐assemble into uniform and stable nanoparticles when heated to above the lower critical solution temperature of the polymer. The amelogenin‐based stimuli‐responsive bioconjugate may be of great use in the fields of bioseparation and drug/gene delivery, and the synthetic approach reported here should provide a convenient means to preparing amelogenin‐based functional biohybrid materials.     

Self‐Assembly of Porphyrin‐Centered Amphiphilic Star Block Copolymer into Polymeric Vesicular Aggregates

Polymeric vesicular aggregates with spherical and tubular shapes were formed from the self‐assembly of a porphyrin‐centered amphiphilic star poly(oxazoline) [poly(phenyloxazoline)‐block‐poly(methyloxazoline)] in an DMF/water mixture containing excess DMF. The aggregates were evaluated by means of UV‐Vis, fluorescent, ¹H NMR spectroscopies, and optical microscopy. The driving force to induce the vesicular aggregates is the interactions between poly(phenyloxazoline) segments which were insoluble in DMF rich aqueous medium.

Polymeric vesicular aggregates with spherical and tubular shapes were formed from the self‐assembly of a porphyrin‐centered amphiphilic star poly(oxazoline) [poly(phenyloxazoline)‐block‐poly(methyloxazoline)] in an DMF/water mixture.     

Synthesis and Self‐Assembly of o‐Nitrobenzyl‐Based Amphiphilic Hybrid Polymer with Light and pH Dual Response

In this paper, novel light‐responsive polyhedral oligomeric silsesquioxane (POSS) end‐capped poly(o‐nitrobenzyl methacrylate) (POSS–PNBMA) are synthesized by the combination of atom transfer radical polymerization (ATRP) and click chemistry. After subsequent partial photocleavage of PNBMA yielding poly(methacrylic acid) (PMAA), pH‐ and light‐responsive random copolymer of POSS–P(NBMA‐co‐MAA) is obtained. The o‐nitrobenzyl‐based amphiphilic hybrid polymer can self‐assemble into spherical micelles in aqueous solution. Hydrophobic POSS and PNBMA segments aggregate into the inner core, and the hydrophilic PMAA chains tend to stretch from the core. The micellar morphology can be tuned by pH changes and UV irradiation. Light irradiation leads to the transformation of P(NBMA‐co‐MAA) into PMAA and to the reorganization of the assemblies, causing the release of encapsulated guest molecule Nile Red into water. This dual‐responsive polymer has a broad potential use in targeted drug delivery.