A triblock copolymer containing the complementary hydrogen bonding recognition pair ureidoguanosine–diaminonaphthyridine (UG–DAN) as pendant functional groups is synthesized using ring‐opening metathesis polymerization (ROMP). The norbornene‐based DAN monomer is shown to allow for a controlled polymerization when polymerized in the presence of a modified‐UG molecule that serves as a protecting group, subsequently allowing for the fabrication of functionalized triblock copolymers. The self‐assembly of the copolymers was characterized using dynamic light scattering and 1H NMR spectroscopy. It is demonstrated that the polymers self‐assemble via complementary hydrogen bonding motifs even at low dilutions, indicating intramolecular interactions.
Hierarchical self‐assembly of transient composite hydrogels is demonstrated through a two‐step, orthogonal strategy using nanoparticle tectons interconnected through metal–ligand coordination complexes. The resulting materials are highly tunable with moduli and viscosities spanning many orders of magnitude, and show promising self‐healing properties, while maintaining complete optical transparency.
The combination of dendritic and linear polymeric structures in the same macromolecule opens up new possibilities for the design of block copolymers and for applications of functional polymers that have self‐assembly properties. There are three main strategies for the synthesis of linear‐dendritic block copolymers (LDBCs) and, in particular, the emergence of click chemistry has made the coupling of preformed blocks one of the most efficient ways of obtaining libraries of LDBCs. In these materials, the periphery of the dendron can be precisely functionalised to obtain functional LDBCs with self‐assembly properties of interest in different technological areas. The incorporation of stimuli‐responsive moieties gives rise to smart materials that are generally processed as self‐assemblies of amphiphilic LDBCs with a morphology that can be controlled by an external stimulus. Particular emphasis is placed on light‐responsive LDBCs. Furthermore, a brief review of the biomedical or materials science applications of LDBCs is presented.
Synthesis of a cyclodextrin (CD) polyrotaxane is achieved for the first time by simultaneous free radical polymerization of isoprene, threading by CD, and stoppering by copolymerization of styrene. This reaction is performed in an eco‐friendly manner in an aqueous medium similar to classical emulsion polymerization. Threaded CD rings of the polyrotaxane are cross‐linked by hexamethylene diisocyanate, leading to highly elastic slide‐ring gels.
The preparation and aqueous self‐assembly of newly Y‐shaped amphiphilic block polyurethane (PUG) copolymers are reported here. These amphiphilic copolymers, designed to have two hydrophilic poly(ethylene oxide) (PEO) tails and one hydrophobic alkyl tail via a two‐step coupling reaction, can self‐assemble into giant unilamellar vesicles (GUVs) (diameter ≥ 1000 nm) with a direct dissolution method in aqueous solution, depending on their Y‐shaped structures and initial concentrations. More interesting, the copolymers can self‐assemble into various distinct nano‐/microstructures, such as spherical micelles, small vesicles, and GUVs, with the increase of their concentrations. The traditional preparation methods of GUVs generally need conventional amphiphilic molecules and additional complicated conditions, such as alternating electrical field, buffer solution, or organic solvent. Therefore, the self‐assembly of Y‐shaped PUGs with a direct dissolution method in aqueous solution demonstrated in this study supplies a new clue to fabricate GUVs based on the geometric design of amphiphilic polymers.
Hierarchical semicrystalline block copolymer nanoparticles are produced in a segmented gas‐liquid microfluidic reactor with top‐down control of multiscale structural features, including nanoparticle morphologies, sizes, and internal crystallinities. Control of multiscale structure on disparate length scales by a single control variable (flow rate) enables tailoring of drug delivery nanoparticle function including release rates.
Colloidal molecules constructed from polymers and nanoparticles (NPs) have recently emerged as a novel class of building blocks for assembling functional hybrid materials. Particularly, self‐assembly of amphiphilic block copolymer (BCP)‐tethered NPs (BNPs) has shown great promise in the nanoscale design of functional hybrid materials. On the one hand, structurally the BNPs can be considered as molecular equivalents that are capable of self‐assembly at multiple hierarchical levels. On the other hand, the assembly of BNPs shows significant differences from molecular assembly due to their large dimension, complex geometry, and multi‐scale interactions involved in the assembly process. The manipulation of BCPs localized near the surface of the NPs offers an effective tool for engineering the interactions between NPs and hence the complexity of NP assembly. In this Feature Article, recent progresses on the self‐assembly of BNPs into functional materials are summarized. First, major strategies for assembling amphiphilic BNPs are highlighted. Secondly, the application of hybrid nanostructures (e.g., vesicles) assembled from BNPs in the field of biomedical imaging and delivery is discussed. Finally, current challenges and perspectives at this frontier are outlined.
Endowing unimolecular soft nanoobjects with biomimetic functions is attracting significant interest in the emerging field of single‐chain technology. Inspired by the compartmentalized structure and polymerase activity of metalloenzymes, copper‐containing compact nanoglobules have been designed, synthesized, and characterized endowed with metalloenzyme mimicking characteristics toward controlled synthesis of water‐soluble polymers and thermoresponsive hydrogels. When compared to metalloenzymes, artificial nanoobjects endowed with metalloenzyme mimicking characteristics offer increased stability against thermal changes and reduced degradability by hydrolytic enzymes.
Self‐assembly of protein–polymer block copolymers is an attractive route for preparing biocatalytic materials. To clarify the effect of bioconjugate shape on self‐assembly without changing the chemical details of either block, four different conjugation sites are selected on the surface of the model globular protein mCherry at residues 3, 108, 131, and 222 to alter the colloidal shape of the bioconjugate. All four mCherry‐b‐poly(N‐isopropylacrylamide) bioconjugates show qualitatively similar phase diagrams, indicating that self‐assembly is robust with respect to changes in conjugation site. However, protein orientation has an effect on the location of the order–disorder transition concentration, and the stability of the disordered micellar phase is shown to be different for each conjugate. Differences in domain spacing also suggest changes in protein orientation within the lamellae.
The preparation of physically crosslinked hydrogels from quasi ABA‐triblock copolymers with a water‐soluble middle block and hydrophobic end groups is reported. The hydrophilic monomer N‐acryloylmorpholine is copolymerized with hydrophobic isobornyl acrylate via a one‐pot sequential monomer addition through reversible addition fragmentation chain‐transfer (RAFT) polymerization in an automated parallel synthesizer, allowing systematic variation of polymer chain length and hydrophobic–hydrophilic ratio. Hydrophobic interactions between the outer blocks cause them to phase‐separate into larger hydrophobic domains in water, forming physical crosslinks between the polymers. The resulting hydrogels are studied using rheology and their self‐healing ability after large strain damage is shown.
In this article, well‐defined cyclic amphiphilic random copolymers bearing azobenzene side chains and pendent carboxyl moieties, cyclic‐P(BHMEm‐co‐AAn)s, are synthesized by combining atom transfer radical polymerization (ATRP) with Cu(I)‐catalyzed azide/alkyne cycloaddition (CuAAC) “click” reaction and selective hydrolysis of tert‐butyl ester. Successful synthesis of the cyclic‐P(BHMEm‐co‐AAn)s is fully characterized and verified via conventional gel permeation chromatography, triple detection gel permeation chromatography, nuclear magnetic resonance, Fourier transform infrared, and matrix‐assisted laser desorption ionization–time‐of‐flight mass spectrometry. The cyclic topology induces profound effects on the glass transition temperatures, self‐assembly behavior, and photoresponsive performance of the copolymers compared with their linear counterparts.
A linear supramolecular polymer based on the self‐assembly of an easily available copillar[5]arene monomer is efficiently prepared, which is evidenced by the NMR spectroscopy, viscosity measurement, and DOSY experiment. The single‐crystal X‐ray analysis reveals that the polymerization of the AB‐type monomer is driven by the quadruple CH•••π interactions and one CH•••O interaction.
Herein, the first example of photosensitive cyclic amphiphilic homopolymers consisting of multiple biphenyl azobenzene chromophores in the cyclic main chain tethered with hydrophilic tetraethylene glycol monomethyl ether units is presented. The synthetic approach involves sequentially performed thermal catalyzed “click” step‐growth polymerization in bulk, and Cu(I)‐catalyzed azide–alkyne cycloaddition (CuAAC) intramolecular cyclization from α‐alkyne/ω‐azide linear precursors. It is observed that such amphiphilic macrocycles exhibit increased glass transition temperatures (Tg), slightly faster trans–cis–trans photoisomerization, and enhanced fluorescence emission intensity compared with the corresponding linear polymers. In addition, the cyclic amphiphilic homopolymers self‐assemble into spherical nanoparticles with smaller sizes which possess slower photoresponsive behaviors in a tetrahydrofuran/water mixture compared with those of the linear ones. All these interesting observations suggest that the cyclic topology has a great influence on the physical properties and self‐assembly behavior of these photoresponsive amphiphilic macrocycles in general.
The directed self‐assembly of gold nanoparticles through the crystallization of surface‐grafted polyethylene oxide (PEO) in ethanol–water mixtures is described. This process is fully reversible and tunable through either the size of the core or the polymeric coating. Characterization by X‐ray scattering and electron microscopy of the self‐assembled structures reveals order at the nanoscale, typically not the case for thermoresponsive gold nanoparticles coated with lower or upper critical solution temperature polymers. A further novelty is the result of selective binding of calcium ions to the PEO in the fluid state: a reversible thermoresponsive transition become irreversible.
The combination of external potential dynamics and Brownian dynamics is introduced to study the kinetics of orientational ordering in block copolymer/superparamagnetic nanoparticle composites where the particles are smaller than the domain spacing and preferentially segregate into one block of the copolymer. This simulation method accounts for both excluded volume interactions and dipolar interactions between particles to quantify alignment kinetics. Two‐dimensional simulations reveal that higher dipolar interaction strengths lead to faster alignment of the block copolymer, where the orientation kinetics obeys an exponential rate law. The observed rate of alignment increases with increasing dipolar interaction strength and is dependent on the initial state of the block copolymer. The primary mechanism of orientational ordering is found to be the redistribution of monomer segments leading to bridging and growth of the block copolymer domains around the nanoparticles.
Polysaccharides are abundant in nature, renewable, nontoxic, and intrinsically biodegradable. They possess a high level of functional groups including hydroxyl, amino, and carboxylic acid groups. These functional groups can be utilized for further modification of polysaccharides with small molecules, polymers, and crosslinkers; the modified polysaccharides have been used as effective building blocks in fabricating novel biomaterials for various biomedical applications such as drug delivery carriers, cell‐encapsulating biomaterials, and tissue engineering scaffolds. This review describes recent strategies to modify polysaccharides for the development of polysaccharide‐based biomaterials; typically self‐assembled micelles, crosslinked microgels/nanogels, three‐dimensional hydrogels, and fibrous meshes. In addition, the outlook is briefly discussed on the important aspects for the current and future development of polysaccharide‐based biomaterials, particularly tumor‐targeting intracellular drug delivery nanocarriers.
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 β‐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.
Well‐defined ABC triblock copolymers based on two hydrophilic blocks, A and C, and a hydrophobic block B are synthesized and their self‐assembly behavior is investigated. Interestingly, at the same solvent, concentration, pH, and temperature, different shape micelles are observed, spherical and worm‐like micelles, depending on the preparation method. Specifically, spherical micelles are observed with bulk rehydration while both spherical and worm‐like micelles are observed with film rehydration.
Polymer‐based crosslinked networks with intrinsic self‐repairing ability have emerged due to their built‐in ability to repair physical damages. Here, novel dual sulfide–disulfide crosslinked networks (s‐ssPxNs) are reported exhibiting rapid and room temperature self‐healability within seconds to minutes, with no extra healing agents and no change under any environmental conditions. The method to synthesize these self‐healable networks utilizes a combination of well‐known crosslinking chemistry: photoinduced thiol‐ene click‐type radical addition, generating lightly sulfide‐crosslinked polysulfide‐based networks with excess thiols, and their oxidation, creating dynamic disulfide crosslinkages to yield the dual s‐ssPxNs. The resulting s‐ssPxN networks show rapid self‐healing within 30 s to 30 min at room temperature, as well as self‐healing elasticity with reversible viscoelastic properties. These results, combined with tunable self‐healing kinetics, demonstrate the versatility of the method as a new means to synthesize smart multifunctional polymeric materials.
Since the development of supramolecular chemical biology, self‐organised nano‐architectures have been widely explored in a variety of biomedical applications. Functionalized synthetic molecules with the ability of non‐covalent assembly in an aqueous environment are typically able to interact with biological systems and are therefore especially interesting for their use in theranostics. Nanostructures based on π‐conjugated oligomers are particularly promising as theranostic platforms as they bear outstanding photophysical properties as well as drug loading capabilities. This Feature Article provides an overview on the recent advances in the self‐assembly of intrinsically fluorescent nanoparticles from π‐conjugated small molecules such as fluorene or perylene based chromophores for biomedical applications.
