Cyclodextrin-Confined Supramolecular Lanthanide Photoswitch.

The utilization of azobenzene-based photoisomerization cannot only control the morphology of supramolecular assemblies, but can also regulate many biological processes. However, the design of azobenzene-involved nanoconstructs with switchable photoluminescence remains challenging because of the light-quenching ability of azobenzene. Herein, an azobenzene-derived multicomponent nanosystem is reported and its function as a supramolecular lanthanide photoswitch is explored. The metal chelation between lanthanide ions (Ln3+  = Eu3+ and Tb3+ ) and 2,6-pyridinedicarboxylic acid is utilized as the light-emitting center but its inherent fluorescence emission is completely suppressed via the disordered motion of the adjoining azophenyl unit. Interestingly, the hydrophobic cavity of α-cyclodextrin can provide a confined microenvironment to immobilize the molecular conformation of trans-azobenzene, thus leading to the recovery of characteristic lanthanide luminescence both in aqueous solution and the hydrogel state. Also, the luminescence can be reversibly turned off when the cis-azobenzene is expelled from the cavity of α-cyclodextrin upon alternating light irradiation. This mutual cooperation arising from host-guest complexation and metal-ligand coordination confers the desired photoswitchable luminescence abilities on the commonly used azobenzenes, which may hold great promise in the creation of more advanced light-responsive smart materials.

Photooxidation-Driven Purely Organic Room-Temperature Phosphorescent Lysosome-Targeted Imaging.

The construction of host-guest-binding-induced phosphorescent supramolecular assemblies has become one of increasingly significant topics in biomaterial research. Herein, we demonstrate that the cucurbit[8]uril host can induce the anthracene-conjugated bromophenylpyridinium guest to form a linear supramolecular assembly, thus facilitating the enhancement of red fluorescence emission by the host-stabilized charge-transfer interactions. When the anthryl group is photo-oxidized to anthraquinone, the obtained linear nanoconstructs can be readily converted into the homoternary inclusion complex, accompanied by the emergence of strong green phosphorescence in aqueous solution. More intriguingly, dual organelle-targeted imaging abilities have been also distinctively achieved in nuclei and lysosomes after undergoing photochemical reaction upon UV irradiation. This photooxidation-driven purely organic room-temperature phosphorescence provides a convenient and feasible strategy for supramolecular organelle identification to track specific biospecies and physiological events in the living cells.

Supramolecular Assembly with Near-Infrared Emission for Two-Photon Mitochondrial Targeted Imaging.

Two-photon supramolecular assembly with near-infrared (NIR) fluorescence emission is constructed from tetraphenylethene derivative possessing methoxyl and vinyl pyridine salt (TPE-2SP), cucurbit[8]uril (CB[8]), and ß-cyclodextrin modified hyaluronic acid (HA-CD). The obtained experimental results indicate that the TPE-2SP exhibits a very weak fluorescence emission at 650 nm, and then complexes with cucurbit[7]uril (CB[7]) to form 1:2 supramolecular pseudorotaxane with an enhanced NIR fluorescence emission at 660 nm. Compared with CB[7], CB[8] can assemble with TPE-2SP to be two-axial netlike pseudopolyrotaxane, resulting in close packing to increase TPE-2SP fluorescence emission with a redshift of 30 nm. Interestingly, TPE-2SP/CB[8] continues to assemble with cancer cell targeting agent HA-CD into nanoparticles, leading to assembling-induced further enhancement of NIR emission. Surprisingly, supramolecular nanoparticles have the two-photon character, and are successfully applied to mitochondrial targeting imaging. This supramolecular assembly system, with two-photon absorption and assembly-induced enhanced NIR luminescence properties, opens new way for biological targeted imaging.

Cucurbituril-Based Biomacromolecular Assemblies.

The construction of controlled biomacromolecular assemblies has become a thriving area of supramolecular chemistry. In this context, cucurbiturils (CBs), a class of macrocyclic receptors having robust skeletons, hydrophobic cavities, and carbonyl-laced portals, have been drawn into the limelight because of their advantageous molecular recognition characteristics with a variety of biomacromolecules, including peptides, nucleic acids, and proteins. In this minireview, we focus on the impressive advances in CB-based biomacromolecular assemblies, such as in biosensors and assays, the regulation of biochemical reactions, and the treatment of serious diseases. CB-promoted subcellular bioimaging has also been demonstrated in different organelles. The case studies presented herein demonstrate the numerous applications, from fundamental research to translational applications, of diverse CB-based supra/biomacromolecular architectures.

Selective binding and controlled release of anticancer drugs by polyanionic cyclodextrins.

The binding stoichiometry, binding constants, and inclusion mode of some water-soluble negatively charged cyclodextrin derivatives, i.e. heptakis-[6-deoxy-6-(3-sulfanylpropanoic acid)]-ß-cyclodextrin(H1), heptakis-[6-deoxy-6-(2-sulfanylacetic acid)]-ß-cyclodextrin(H2), mono-[6-deoxy-6-(3-sulfanylpropanoic acid)]-ß-cyclodextrin (H3) and mono-[6-deoxy-6-(2-sulfanylacetic acid)]-ß-cyclodextrin (H4), with three anticancer drugs, i.e. irinotecan hydrochloride; topotecan hydrochloride; doxorubicin hydrochloride, were investigated by means of 1H NMR, UV-Vis spectroscopy, mass spectra and 2D NMR. Polyanionic cyclodextrins H1-H2 showed the significantly high binding abilities of up to 2.6 × 104-2.0 × 105 M-1 towards the selected anticancer drugs, which were nearly 50-1000 times higher than the corresponding Ks values of native ß-cyclodextrin. In addition, these polyanionic cyclodextrins also showed the pH-controlled release behaviors. That is, the anticancer drugs could be efficiently encapsulated in the cyclodextrin cavity at a pH value similar to that of serum but sufficiently released at an endosomal pH value of a cancer cell, which would make these cyclodextrin derivatives the potential carriers for anticancer drugs.

A tunable full-color lanthanide noncovalent polymer based on cucurbituril-mediated supramolecular dimerization.

The construction of lanthanide multicolor luminescent materials with tunable photoluminescence properties has been developed as one of the increasingly significant topics and shown inventive applications in miscellaneous fields. However, fabricating such materials based on synergistically assembly-induced emission rather than simple blending of different fluorescent dyes together still remains a challenge. Herein, we report a europium-based noncovalent polymer with tunable full-color emission, which is constructed from the 2,6-pyridinedicarboxylic acid-bearing bromophenylpyridinium salt. This rationally designed bifunctional component can concurrently serve as a guest molecule and a chelating ligand to associate with cucurbit[8]uril and europium ions, thus leading to the formation of a trichromatic (red-green-blue, RGB) photoluminescent polypseudorotaxane-type noncovalent polymer in aqueous solution. Meanwhile, the full-color emission enclosed within the RGB color triangle could be readily produced by simply tuning the molar ratio of cucurbit[8]uril and europium ions. The lanthanide supramolecular polymer featuring tricolor emission, long lifetime, high photoluminescence efficiency and low cytotoxicity could be further applied in multicolor imaging in a cellular environment. These results provide a new and feasible strategy for the construction of full-color single lanthanide self-assembled nanoconstructs.

Highly efficient photocontrolled targeted delivery of siRNA by a cyclodextrin-based supramolecular nanoassembly.

In this study, we have constructed a binary supramolecular nanoassembly composed of α-cyclodextrin-modified hyaluronic acid and an azobenzene-modified diphenylalanine derivative with a positively charged imidazole group. This nanoassembly can bind with siRNA through electrostatic interactions and efficiently delivered them into cancer cells and inhibited their growth.

Drug Displacement Strategy for Treatment of Acute Liver Injury with Cyclodextrin-Liposome Nanoassembly.

Biofunctional supramolecular assemblies that combine macrocyclic receptors and amphiphiles are potent drug delivery systems, but optimization and implementation challenges remain. We herein describe a cooperative drug displacement strategy exemplified by the use of cyclodextrin-liposome supramolecular nanoassemblies as a therapy for acute liver injury. The hepatoprotective drug silibinin was solubilized in phosphotyramine-modified ß-cyclodextrin, and subsequent encapsulation of the silibinin-cyclodextrin complex in phosphatidylcholine liposomes gave uniformly sized and stable nanoassemblies that accumulated preferentially in the liver of mice. Enzymatic cleavage of the phosphate ester of the ß-cyclodextrin resulted in rapid release of the encapsulated silibinin. Significantly, silibinin could be readily displaced by cytotoxic bile acids, thus leading to the removal of excess bile acids from the bodies of mice and the recovery of liver function. Our results demonstrate that cyclodextrin-based nanoassemblies with a dual role of solubilizing a drug and removing toxins constitute a promising therapy for hepatic injury.