Dual-Responsive Drug-Delivery System Based on PEG-Functionalized Pillararenes Containing Disulfide and Amido Bonds for Cancer Theranostics

The construction of a smart drug-delivery system based on amphiphilic pillararenes with multiple responsiveness properties has become an important way to improve the efficacy of tumor chemotherapy. Here, a new PEG-functionalized pillararene (EtP5-SS-PEG) containing disulfide and amido bonds was designed and synthesized, which has been used to construct a novel supramolecular nanocarrier through a host-guest interaction with a perylene diimide derivative (PDI-2NH₄) and their supramolecular self-assembly. This nanocarrier showed good drug loading capability, and dual stimulus responsiveness to enzyme and GSH (glutathione). After loading of doxorubicin (DOX), the prepared nanodrugs displayed efficient DOX release and outstanding cancer theranostics ability.     

Functionalized Fluorescent Organic Nanoparticles Based AIE Enabling Effectively Targeting Cancer Cell Imaging

We report a fluorescent dye TM by incorporating the tetraphenylethylene (TPE) and cholesterol components into perylene bisimides (PBI) derivative. Fluorescence emission spectrum shows that the dye has stable red emission and aggregation-induced emission (AIE) characteristics. The incorporation of cholesterol components triggers TM to show induced chirality through supramolecular self-assembly. The cRGD-functionalized nanoparticles were prepared by encapsulating fluorescent dyes with amphiphilic polymer matrix. The functionalized fluorescent organic nanoparticles exhibit excellent biocompatibility, large Stokes’ shift and good photostability, which make them effective fluorescent probes for targeting cancer cells with high fluorescence contrast.     

A novel helical chainlike nickel(II) coordination polymer containing 1D trigonal channels with water molecule guests

A novel 1D helical nickel coordination polymer, [Ni(TAU)₂(4,4′-bipy)]_n·2nH₂O (TAU = taurine, 4,4′-bipy = 4,4′-bipyridine), was synthesized and its crystal structure has been determined by X-ray diffraction. Each helix interlinks with six adjacent helices through extensive hydrogen bonds to form 3D supramolecular structure, in which 1D trigonal microporous channels filled with water guest molecules exist within the polymer coils. The framework remains intact on removal of guest water molecules which is proved by XPRD and TGA. Variable temperature magnetic susceptibility indicates weak anti-ferromagnetic interactions between the Ni(II) ions.     

四苯乙烯衍生物的合成及聚集诱导发光性质

以2,2'-联吡啶(Bpy)为母体,通过Suzuki偶联反应在其5位和5'位引入了四苯乙烯(TPE)基团,设计合成了5-四苯乙烯-2,2'-联吡啶(Bpy-1TPE)和5,5'-二四苯乙烯-2,2'-联吡啶(Bpy-2TPE)两个具有聚集诱导发光(AIE)性质的荧光分子。经1HNMR、13CNMR及EA对目标产物进行了结构测试,并考察了其紫外-可见吸收、荧光发射、AIE、压致变色性以及结构与性质之间的构效关系。结果表明:相对于具有1个四苯乙烯单元的Bpy-1TPE,含2个四苯乙烯单元的Bpy-2TPE共轭体系更大且电荷呈对称分布,能隙宽度较低,其在二氯甲烷溶液中的最大发射峰由483 nm红移至490 nm。Bpy-2TPE表现出明显的AIE性质和压致变色性质,其固体样品经研磨后最大发射波长可由485 nm红移至500 nm。     

"Host-guest" chemistry in the synthesis of ordered nonsiliceous mesoporous materials

On the basis of the consideration of "host-guest" chemistry, the interactions between guest molecules are highlighted in the synthesis of nonsiliceous mesoporous materials by the "soft-template" and "hard-template" approaches. A generalized "acid-base pair" concept is utilized in selecting appropriate guest molecules to prepare highly ordered mesoporous metal oxides, phosphates, and borates with diversified structures. Mesoscopically ordered polymer and carbon frameworks with uniformly large pore sizes are derived from the self-assembly of an organic surfactant with an organic guest. Properly building the guest unit and decorating the host are important in replicating ordered nonsiliceous single-crystal nanoarrays. Outlooks on the potential possibilities for synthesizing ordered mesoporous nonsiliceous materials are presented as well.     

A New Thermo‐, pH‐ and CO2‐Responsive Fluorescent Four‐Arm Star Polymer with Aggregation‐Induced Emission for Long‐Term Cellular Tracing

Development of fluorescent bioprobes for long‐term cell tracking is of great importance to monitor the processes of genesis, development, invasion, and metastasis of cancerous cells. Herein, a new multistimuli‐responsive star polymer of tetraphenylethene‐graft‐tetra‐poly[N‐[2‐(diethylamino)‐ethyl]acrylamide] (TPE‐tetraPDEAEAM) with aggregation‐induced emission (AIE) effect for tracing live cells over a long period of time is synthesized by atom transfer radical polymerization using TPE derivative as initiator. TPE‐tetraPDEAEAM gives both lower critical solution temperature and fluorescence responses to the stimulus of the temperature, pH, and CO₂ by combining the thermoresponsive and pH/CO₂‐responsive moieties of the diethylamino and acrylamide groups. The AIE‐active TPE‐tetraPDEAEAM has the advantages of very low cytotoxicity, efficient cellular uptake, and strong fluorescence of polymer‐treated cells, which ensure its good performance in long‐term cell tracing. This facile tracking of HeLa cells for as long as nine passages exhibits superior performance in long‐term cell tracing as compared with some commercial cell tracing probes.     

FRET-Based In-Cell Detection of Highly Selective Supramolecular Complexes of meso-Tetraarylporphyrin with Peptide/BODIPY-Modified Per-O-Methyl-β-Cyclodextrins

Artificial supramolecular systems capable of self-assembly and that precisely function in biological media are in high demand. Herein, we demonstrate a highly specific host-guest-pair system that functions in living cells. A per-O-methyl-β-cyclodextrin derivative (R8-B-CD^Me) bearing both an octaarginine peptide chain and a BODIPY dye was synthesized as a fluorescent intracellular delivery tool. R8-B-CD^Me was efficiently taken up by HeLa cells through both endocytosis and direct transmembrane pathways. R8-B-CD^Me formed a 2 : 1 inclusion complex with tetrakis(4-sulfonatophenyl)porphyrin (TPPS) as a guest molecule in water, from which fluorescence resonance energy transfer (FRET) from R8-B-CD^Me to TPPS was observed. The FRET phenomenon was clearly detected in living cells using confocal microscopy techniques, which revealed that the formed supramolecular R8-B-CD^Me/TPPS complex was maintained within the cells. The R8-B-CD^Me cytotoxicity assay revealed that the addition of TPPS counteracts the strong cytotoxicity (IC₅₀=16 μM) of the CD cavity due to complexation within the cells. A series of experiments demonstrated the bio-orthogonality of the supramolecular per-O-methyl-β-CD/tetraarylporphyrin host-guest pair in living cells.     

Block copolymer aggregates with photo-responsive switches: Towards a controllable supramolecular container

Herein, we present a concept of combining host-guest chemistry with block copolymer self-assembly to fabricate an inner cross-linking block copolymer aggregate with photo-responsive switches on the basis of the reversible interaction between azobenzene and β-cyclodextrin, which can serve as a controllable supramolecular container to load and release guest molecules reversibly. The inner cross-link makes the block copolymer aggregates exhibit good stability, and the aggregates can keep their spherical morphologies during photo-irradiation treatment. When the switches are in on-state, cyclodextrins can bind with hydrophobic pyrene molecules; and when the switches are in off-state, pyrene molecules will get away from the cyclodextrins. The photo-controllable switches embedded in the aggregates endow this new supramolecular container with the capability to load and release guest molecules reversibly without structure disruption. It is anticipated that this line of work may open an avenue for fabricating new polymeric containers which can be used for controllable molecular transfer and catalysis.     

Polymer Gels Constructed Through Metal–Ligand Coordination

In the past few years, combining supramolecular and macromolecular chemistries has become of great interest to yield dynamic and responsive assemblies with self-restructuring abilities. Among them, polymer networks, that are held together by one or a combination of supramolecular interactions, offer new possibilities to scientists for the creation of artificial materials with self-healing properties. In particular, incorporating coordination complexes into polymeric architectures opens up the possibility of imparting the physicochemical properties of both partners to the resulting material. Here, recent achievements in the field of supramolecular gels that are formed via self-assembly of oligo- and polymeric units through reversible metal–ligand interactions are reviewed. The different strategies and routes for the elaboration of those materials are reported as well as the properties that the coordination centers confer to the supramolecular assemblies.     

Exploring the complexity of supramolecular interactions for patterning at the liquid-solid interface

The use of self-assembly to fabricate surface-confined adsorbed layers (adlayers) from molecular components provides a simple means of producing complex functional surfaces. The molecular self-assembly process relies on supramolecular interactions sustained by noncovalent forces such as van der Waals, electrostatic, dipole-dipole, and hydrogen bonding interactions. Researchers have exploited these noncovalent bonding motifs to construct well-defined two-dimensional (2D) architectures at the liquid-solid interface. Despite myriad examples of 2D molecular assembly, most of these early findings were serendipitous because the intermolecular interactions involved in the process are often numerous, subtle, cooperative, and multifaceted. As a consequence, the ability to tailor supramolecular patterns has evolved slowly. Insight gained from various studies over the years has contributed significantly to the knowledge of supramolecular interactions, and the stage is now set to systematically engineer the 2D supramolecular networks in a "preprogrammed" fashion. The control over 2D self-assembly of molecules has many important implications. Through appropriate manipulation of supramolecular interactions, one can "encode" the information at the molecular level via structural features such as functional groups, substitution patterns, and chiral centers which could then be retrieved, transferred, or amplified at the supramolecular level through well-defined molecular recognition processes. This ability allows for precise control over the nanoscale structure and function of patterned surfaces. A clearer understanding and effective use of these interactions could lead to the development of functional surfaces with potential applications in molecular electronics, chiral separations, sensors based on host-guest systems, and thin film materials for lubrication. In this Account, we portray our various attempts to achieve rational design of self-assembled adlayers by exploiting the aforementioned complex interactions at the liquid-solid interface. The liquid-solid interface presents a unique medium to construct flawless networks of surface confined molecules. The presence of substrate and solvent provides an additional handle for steering the self-assembly of molecules. Scanning tunneling microscopy (STM) was used for probing these molecular layers, a technique that serves not only as a visualization tool but could also be employed for active manipulation of molecules. The supramolecular systems described here are only weakly adsorbed on a substrate, which is typically highly oriented pyrolytic graphite (HOPG). Starting with fundamental studies of substrate and solvent influence on molecular self-assembly, this Account describes progressively complex aspects such as multicomponent self-assembly via 2D crystal engineering, emergence, and induction of chirality and stimulus responsive supramolecular systems.     

Fabrication and microwave absorption properties of size-controlled polymer/Fe<Subscript>3</Subscript>O<Subscript>4</Subscript>hybrid microsphere based on aggregation-induced emission active polyarylene ether nitrile

The article fabricated novel polymer/magnetic hybrid microspheres via solvothermal method by using ferroferric oxide (Fe₃O₄) and aggregation-induced emission (AIE) active polyarylene ether nitrile (PEN) as building components. The PEN was copolymerized through phenolphthalin and AIE-gen (4, 4′-(1, 2-di (4-hydroxyphenyl)-1, 2-diyl) diphenol), wherein AIE-gen endowed the copolymer with AIE effect so that the copolymer could aggregate correspondingly in different solvent/nonsolvent systems and produce fluorescence enhanced. In these experiments, the diameter of Fe₃O₄/PEN hybrid microspheres was controlled by the volume proportion of nonsolvent (ethylene glycol (EG)) and solvent (N-methyl pyrrolidone (NMP)) in preparation process based on the aggregation behavior of AIE active PEN. Moreover, the resulted hybrid microspheres also had excellent magnetic and electromagnetic absorption performance. Specifically, they all exhibited a strong reflection loss peak both in the low and high frequency range. Meanwhile, with the change of coating thickness, these hybrid microspheres had a wide wave-absorbing frequency from 5 GHz to16 GHz. The results supported that the hybrid microspheres integrated with magnetism and AIE property will have a wide application in the preparation and improvement of size-controlled inorganic organic nanocomposites.     

Responsive nanostructures from aqueous assembly of rigid-flexible block molecules

During the past decade, supramolecular nanostructures produced via self-assembly processes have received considerable attention because these structures can lead to dynamic materials. Among these diverse self-assembly systems, the aqueous assemblies that result from the sophisticated design of molecular building blocks offer many potential applications for producing biocompatible materials that can be used for tissue regeneration, drug delivery, and ion channel regulation. Along this line, researchers have synthesized self-assembling molecules based on ethylene oxide chains and peptide building blocks to exploit water-soluble supramolecular structures. Another important issue in the development of systems that self-assemble is the introduction of stimuli-responsive functions into the nanostructures. Recently, major efforts have been undertaken to develop responsive nanostructures that respond to applied stimuli and dynamically undergo defined changes, thereby producing switchable properties. As a result, this introduction of stimuli-responsive functions into aqueous self-assembly provides an attractive approach for the creation of novel nanomaterials that are capable of responding to environmental changes. This Account describes recent work in our group to develop responsive nanostructures via the self-assembly of small block molecules based on rigid-flexible building blocks in aqueous solution. Because the rigid-flexible molecules self-assemble into nanoscale aggregates through subtle anisometric interactions, the small variations in local environments trigger rapid transformation of the equilibrium features. First, we briefly describe the general self-assembly of the rod amphiphiles based on a rigid-flexible molecular architecture in aqueous solution. We then highlight the structural changes and the optical/macroscopic switching that occurs in the aqueous assemblies in response to the external signals. For example, the aqueous nanofibers formed through the self-assembly of the rod amphiphiles respond to external triggers by changing their shape into nanostructures such as hollow capsules, planar sheets, helical coils, and 3D networks. When an external trigger is applied, supramolecular rings laterally associate and merge to form 2D networks and porous capsules with gated lateral pores. We expect that the combination of self-assembly principles and responsive properties will lead to a new class of responsive nanomaterials with many applications.     

Polyoxometalate-cucurbituril molecular solid as photocatalyst for dye degradation under visible light

An organic-inorganic hybrid molecular solid based on Lindqvist-type polyoxometalate (POM) anions, {W₆O₁₉}^2 −, and decamethylcucurbit[5]uril (Me₁₀CB[5]) was synthesized under hydrothermal condition. In the structure of {[Na₂(W₆O₁₉)(Me₁₀CB[5])(H₂O)]·2H₂O}_n (complex 1), the sodium cations, {W₆O₁₉}^2 − anions, and Me₁₀CB[5] macrocycles formed a 1D chain subunit that assembled into a 3D supramolecular host-guest network through extensive supramolecular interactions. Furthermore, the complex displayed enhanced photocatalytic activity towards the degradation of rhodamine B (RhB) in water under visible light irradiation.     

Cucurbit[n]uril Host-Guest Complexes of Acids,Photoacids, and Super Photoacids

The supramolecular chemistry of host-guest complexes of cucurbit[n]urils (CB[n]) with acidic guests in the ground (HG⁺) and excited states (HG⁺*) are reviewed. The effects of CB[n] complexation on the guests’ pK_a and/or pK_a* values are related to relative binding constants and host-guest structures of the acid form of the guest and its conjugate base. Included are carbon acids, guests of biological and medicinal interest, dyes and related polyaromatic guests, and other organic and organometallic guests. The applications of the pK_a shifts to the solubility, stability, and bioavailabilty of drug molecules, the stability and enhanced spectral properties of dyes, and in pH-induced self-sorting, micelle formation, host-guest shuttling, and controlled guest release, are discussed.     

Guest-responsive,Non-proteolytic Harvest of a Cell-sheet using Controllable Host-guest Chemistry

A new non-proteolytic method to harvest a cell-sheet was demonstrated using controllable host-guest interactions which can be dissociated by treating a strong guest on demand. Fibroblast cells (NIH3T3) were grown to confluence on a 1,6-diammoniumhexane conjugated hyaluronic acid (DAH-HA) polymer which was anchored to a cucurbit[7]uril (CB[7]) surface using the host-guest interaction between DAH and CB[7]. Treating with a strong guest allowed the cultured cells to be detached from the surface as a free standing sheet. This approach demonstrated the great potential of controllable host-guest chemistry as a novel tool for non-proteolytic harvesting of cell-sheets useful for regenerative therapy.     

Dual stimuli-responsive supramolecular polymeric nanoparticles based on poly(<Emphasis Type="Italic">α</Emphasis>-cyclodextrin) and acetal-modified <Emphasis Type="Italic">β</Emphasis>-cyclodextrin-azobenzene

To aim at pH environment in tumor tissue and light-controlled drug release, UV and pH dual-responsive supramolecular polymeric nanoparticles mediated by host-guest interactions of poly(α-cyclodextrin) and acetal-modified β-cyclodextrin-azobenzene were developed in this work. The host molecule was poly(α-cyclodextrin) and the guest molecule was composed of acetal-modified β-cyclodextrin with one azobenzene linked. The inclusion of α-cyclodextrin and azobenzene leaded to amphiphilic supramolecular polymer, which further self-assembled to form supramolecular polymeric nanoparticles in aqueous medium. UV and pH responsiveness of supramolecular polymeric nanoparticles attributed to azobenzene and acetal, respectively. Supramolecular polymeric nanoparticles based on poly(α-cyclodextrin) and acetal-modified β-cyclodextrin-azobenzene with the average diameter of sub-100 nm were controllable to release the drugs regulated by pH and UV.     

Supramolecular approach for synthesis and functionalization of cyclic macromolecules

This report highlights our recent findings concerning the synthesis of cyclic polymers based on supramolecular chemistry as well as the stereochemical recognition of helices by a cyclic macromolecule consisting of helical peptides and porphyrins. The first part will focus on an electrostatic self-assembly and covalent fixation strategy for the efficient synthesis of cyclic polymers. It has been shown that a unimeric polymer assembly is formed exclusively from the linear polymer precursor having cyclic ammonium salt end groups carrying dicarboxylate counter ions. An effective synthesis of cyclic polymers has been achieved by the subsequent covalent transformation of the ammonium salt groups. The process has been extended to the synthesis of cyclic macromonomers, which produced a unique polymer network having both covalent and mechanical linkages. The second part will focus on the stereochemical recognition of helices by a cyclic host. α-Aminoisobutyric acid (Aib) peptide-based cyclic hosts having metalloporphyrin units have been synthesized for guest binding and chiroptical sensing. By using these cavities, biologically important “peptide bundling” has been realized through complexation of helical peptide guests, where the three helical chains, two of which are from the host and one from the guest, are harmonized stereochemically in a confined cavity, leading to intense chiroptical outputs in the absorption bands of the metalloporphyrin units. The selective peptide bundling events based on helical senses of the host/guest molecules has also been achieved with a chiral conformational matching.     

Stimuli-Responsive Cucurbit[n]uril-Mediated Host-Guest Complexes on Surfaces

Supramolecular functional surfaces are at the heart of many materials and medical applications. Increasing interest can be seen for devising new supramolecular functionalization strategies of surfaces. In this review we place particular emphasis on the use of cucurbit[n]uril-mediated host-guest complexation as surface functionalization strategy. The state of the art of cucurbit[n]uril-mediated host-guest complexes on surfaces is reviewed. Cucurbit[n]urils (CB[n]) are able to form strong host-guest complexes with affinities that span several orders of magnitudes up to the regime of the biotin-streptavidin pair and that can be modulated by applying remote stimuli provided suitably sensitive guests were selected. Strategies to fabricate stimuli-responsive surfaces creates versatile supramolecular systems and several applications of these types of surfaces are outlined.     

Healable supramolecular polymer solids

The reversible nature of non-covalent interactions between constituting building blocks permits one to temporarily disassemble supramolecular polymers through the application of an appropriate external stimulus “on command”. This framework has recently emerged as a general design strategy for the development of healable polymer systems. The approach exploits that the temporary disassembly decreases the molecular weight and in the case of cross-linked polymers the cross-link density, and thereby causes an increase of the chain mobility and a reduction of the viscosity of the material. The transformation thus enables the disassembled material to flow and fill defects, before the original supramolecular polymer is re-assembled. Focusing on recent progress in the area of healable supramolecular polymer solids based on hydrogen-bonding, metal-ligand and π–π interactions, as well as supramolecular nanocomposites, this review article summarizes the development and current state of the field.     

Dual-Targeted Supramolecular Vesicles Based on the Complex of Galactose Capped Pillar[5]Arene and Triphenylphosphonium Derivative for Drug Delivery

In this study, a dual targeted supramolecular glycol-vesicle based on the host-guest complexation of galactose capped pillar[5]arene ( GALWP5 ) and triphenylphosphonium derivative ( D-TPP ) have been constructed ( GALWP5⊃D-TPP ), which showed dual target potential (cell and mitochondria targeting) resulting from its galactose units and TPP units, respectively. The dual targeted glycol-vesicle displays ignorable cytotoxicity and good mitochondria targeting. Our work presents a good example of rational design for an effective cell and subcellular organelles dual targeted delivery system.