Tuning the Amphiphilicity of Building Blocks: Controlled Self‐Assembly and Disassembly for Functional Supramolecular Materials

Amphiphilicity is one of the molecular bases for self‐assembly. By tuning the amphiphilicity of building blocks, controllable self‐assembly can be realized. This article reviews different routes for tuning amphiphilicity and discusses different possibilities for self‐assembly and disassembly in a controlled manner. In general, this includes irreversible and reversible routes. The irreversible routes concern irreversible reactions taking place on the building blocks and changing their molecular amphiphilicity. The building blocks are then able to self‐assemble to form different supramolecular structures, but cannot remain stable upon loss of amphiphilicity. Compared to the irreversible routes, the reversible routes are more attractive due to the good control over the assembly and disassembly of the supramolecular structure formed via tuning of the amphiphilicity. These routes involve reversible chemical reactions and supramolecular approaches, and different external stimuli can be used to trigger reversible changes of amphiphilicity, including light, redox, pH, and enzymes. It is anticipated that this line of research can lead to the fabrication of new functional supramolecular assemblies and materials.     

25th Anniversary Article: Reversible and Adaptive Functional Supramolecular Materials: “Noncovalent Interaction” Matters

Supramolecular materials held together by noncovalent interactions, such as hydrogen bonding, host–guest interactions, and electrostatic interactions, have great potential in material science. The unique reversibility and adaptivity of noncovalent intreractions have brought about fascinating new functions that are not available by their covalent counterparts and have greatly enriched the realm of functional materials. This review article aims to highlight the very recent and important progresses in the area of functional supramoleuclar materials, focusing on adaptive mechanical materials, smart sensors with enhanced selectivity, soft luminescent and electronic nanomaterials, and biomimetic and biomedical materials with tailored structures and functions. We cannot write a complete account of all the interesting work in this area in one article, but we hope that it can in a way reflect the current situation and future trends in this prosperously developing area of functional supramolecular materials.     

Controlled Fabrication of Micropatterned Supramolecular Gels by Directed Self‐Assembly of Small Molecular Gelators

Herein, the micropatterning of supramolecular gels with oriented growth direction and controllable spatial dimensions by directing the self‐assembly of small molecular gelators is reported. This process is associated with an acid‐catalyzed formation of gelators from two soluble precursor molecules. To control the localized formation and self‐assembly of gelators, micropatterned poly(acrylic acid) (PAA) brushes are employed to create a local and controllable acidic environment. The results show that the gel formation can be well confined in the catalytic surface plane with dimensions ranging from micro‐ to centimeter. Furthermore, the gels show a preferential growth along the normal direction of the catalytic surface, and the thickness of the resultant gel patterns can be easily controlled by tuning the grafting density of PAA brushes. This work shows an effective “bottom‐up” strategy toward control over the spatial organization of materials and is expected to find promising applications in, e.g., microelectronics, tissue engineering, and biomedicine.     

A Supramolecular Approach to Enzyme Immobilization in Micro‐Channels

A supramolecular assembly scheme is developed to enable the facile in‐situ immobilization of enzymes in a microfluidic channel system. A combination of orthogonal supramolecular interactions of host (β‐cyclodextrin)–guest (adamantane) and biotin–Streptavidin (SAv) interactions are employed to generate reusable homogeneous enzyme layers in microchannels. The structural integrity and catalytic activity of the immobilized enzyme calf‐intestine alkaline phosphatase (AlkPh) is demonstrated. From the kinetic analysis of a dephosphorylation reaction, the specificity constant k_cat/K_M for immobilized alkaline phosphatase in the channels is on the order of 10⁵ M^?1s^?1 and comparable to known literature values in other environments. These observations are ascribed to the good access of the substrate to favorably oriented enzymes across the microchannel. Therefore, this study demonstrates the great potential for adopting a supramolecular assembly scheme to immobilize enzymes in microfluidic devices.     

Bioinspired Diselenide‐Bridged Mesoporous Silica Nanoparticles for Dual‐Responsive Protein Delivery

Controlled delivery of protein therapeutics remains a challenge. Here, the inclusion of diselenide‐bond‐containing organosilica moieties into the framework of silica to fabricate biodegradable mesoporous silica nanoparticles (MSNs) with oxidative and redox dual‐responsiveness is reported. These diselenide‐bridged MSNs can encapsulate cytotoxic RNase A into the 8–10 nm internal pores via electrostatic interaction and release the payload via a matrix‐degradation controlled mechanism upon exposure to oxidative or redox conditions. After surface cloaking with cancer‐cell‐derived membrane fragments, these bioinspired RNase A‐loaded MSNs exhibit homologous targeting and immune‐invasion characteristics inherited from the source cancer cells. The efficient in vitro and in vivo anti‐cancer performance, which includes increased blood circulation time and enhanced tumor accumulation along with low toxicity, suggests that these cell‐membrane‐coated, dual‐responsive degradable MSNs represent a promising platform for the delivery of bio‐macromolecules such as protein and nucleic acid therapeutics.     

A Dual‐Responsive Mesoporous Silica Nanoparticle for Tumor‐Triggered Targeting Drug Delivery

A novel pH‐ and redox‐ dual‐responsive tumor‐triggered targeting mesoporous silica nanoparticle (TTTMSN) is designed as a drug carrier. The peptide RGDFFFFC is anchored on the surface of mesoporous silica nanoparticles via disulfide bonds, which are redox‐responsive, as a gatekeeper as well as a tumor‐targeting ligand. PEGylated technology is employed to protect the anchored peptide ligands. The peptide and monomethoxypolyethylene glycol (MPEG) with benzoic‐imine bond, which is pH‐sensitive, are then connected via “click” chemistry to obtain TTTMSN. In vitro cell research demonstrates that the targeting property of TTTMSN is switched off in normal tissues with neutral pH condition, and switched on in tumor tissues with acidic pH condition after removing the MPEG segment by hydrolysis of benzoic‐imine bond under acidic conditions. After deshielding of the MPEG segment, the drug‐loaded nanoparticles are easily taken up by tumor cells due to the exposed peptide targeting ligand, and subsequently the redox signal glutathione in tumor cells induces rapid drug release intracellularly after the cleavage of disulfide bond. This novel intelligent TTTMSN drug delivery system has great potential for cancer therapy.