Cyclodextrin Metal-Organic Framework as a Broad-Spectrum Potential Delivery Vehicle for the Gasotransmitters.

The important role of gasotransmitters in physiology and pathophysiology suggest employing gasotransmitters for biomedical treatment. Unfortunately, the difficulty in storage and controlled delivery of these gaseous molecules hindered the development of effective gasotransmitters-based therapies. The design of a safe, facile, and wide-scale method to delivery multiple gasotransmitters is a great challenge. Herein, we use an ultrasonic assisted preparation γ-cyclodextrin metal organic framework (γ-CD-MOF) as a broad-spectrum delivery vehicle for various gasotransmitters, such as SO2, NO, and H2S. The release rate of gasotransmitters could be tuned by modifying the γ-CD-MOF with different Pluronics. The biological relevance of the exogenous gasotransmitters produced by this method is evidenced by the DNA cleavage ability and the anti-inflammatory effects. Furthermore, the γ-CD-MOF composed of food-grade γ-CD and nontoxic metal salts shows good biocompatibility and particle size (180 nm). Therefore, γ-CD-MOF is expected to be an excellent tool for the study of co-delivery and cooperative therapy of gasotransmitters.

Green Synthesis of Indeno[1,2-b]quinoxalines Using ß-Cyclodextrin as Catalyst.

An efficient, mild, and green method was developed for the synthesis of indeno[1,2-b]quinoxaline derivatives via o-phenylenediamine (OPD) and 2-indanone derivatives utilizing ß-cyclodextrin (ß-CD) as the supramolecular catalyst. The reaction can be carried out in water and in a solid state at room temperature. ß-CD can also catalyze the reaction of indan-1,2-dione with OPD with a high degree of efficiency. Compared to the reported methods, this procedure is milder, simpler, and less toxic, making it an eco-friendly alternative. In addition, the ß-CD can be recovered and reused without the loss of activity.

Recent Advances of Porous Materials Based on Cyclodextrin.

Porous materials have attracted significant attention because of their rising applications in many fields. Cyclodextrins (CDs) are suitable building units in the fabrication of porous materials owing to their intrinsic nanoporous structure, easy modification, and biocompatibility, which may result in the formation of CD-based organic frameworks (including cyclodextrin metal-organic frameworks (CD-MOFs) and cyclodextrin covalent organic frameworks (CD-COFs)), and CD-based polymer hybrid porous materials. This review focuses on the recent progress in the fabrication and applications of CD-based porous materials with novel structures and functionalities.

Functional materials with self-healing properties: a review.

Self-healing materials (SHMs) have been a research hot topic in recent years owing to their greatly improved longevity and safety in practical applications. Recently, research on SHMs has gradually expanded from structural materials to functional materials. Functional materials with self-healing properties (FMSH) require simultaneous repairing not only of the mechanical properties but of the functionalities from damaged cracks or wounds. It is more challenging to introduce both self-healing properties and a particular functionality to materials owing to the difficulties of preparing the materials and their more complex healing mechanism. Herein, we summarize the recent progress that has been made in FMSH, put forward insights from the perspectives of material preparation and healing mechanisms and highlight future developments for FMSH.

Semi-IPNs with Moisture-Triggered Shape Memory and Self-Healing Properties.

Moisture or water has the advantages of being green, inexpensive, and moderate. However, it is challenging to endow water-induced shape memory property and self-healing capability to one single polymer because of the conflicting structural requirement of the two types of materials. In this study, this problem is solved through introducing two kinds of supramolecular interactions into semi-interpenetrating polymer networks (semi-IPNs). The hydrogen bonds function as water-sensitive switches, making the materials show moisture-induced shape memory effect. The host-guest interactions (ß-cyclodextrin-adamantane) serve as both permanent phases and self-healing motifs, enabling further increased chain mobility at the cracks and self-healing function. In addition, these polyvinylpyrrolidone/poly(hydroxyethyl methacrylate-co-butyl acrylate) semi-IPNs also show thermosensitive triple-shape memory effect.

Electromagnetic Wave Absorption Coating Material with Self-Healing Properties.

Electromagnetic wave absorption coatings can effectively minimize electromagnetic radiation and are widely used in the military and civil field. However, even small scratches on the coating can lead to a large decline of absorption ability and bring serious consequences. To enhance the lifetime of electromagnetic wave absorbing coating, a kind of self-healing electromagnetic wave absorbing coating is developed by introducing host-guest interactions between the absorbing fillers and polymer matrix. After being damaged, the cracks on this coating can be healed completely with the aid of small amounts of water. Simultaneously, the electromagnetic absorbing ability of the coating is restored along with the self-healing process.

A Tri-Stimuli-Responsive Shape-Memory Material Using Host-Guest Interactions as Molecular Switches.

A thermo-, photo- and chemoresponsive shape-memory material is successfully prepared by introducing α-cyclodextrin (αCD) and azobenzene (Azo) into a poly(acrylate acid)/alginate (PAA/Alg) network. The tri-stimuli-responsive formation/dissociation of αCD-Azo acts as molecular switches freezing or increasing the molecular mobility. The resulting film herein can be processed into temporary shapes as needed and recovers its initial shape upon the application of light irradiation, heating, or chemical agent independently. Furthermore, the agar diffusion test suggests that the α-CD-Alg/Azo-PAA has good biocompatibility for L929 fibroblast-like cells.

Conductive elastomers with autonomic self-healing properties.

Healable, electrically conductive materials are highly desirable and valuable for the development of various modern electronics. But the preparation of a material combining good mechanical elasticity, functional properties, and intrinsic self-healing ability remains a great challenge. Here, we design composites by connecting a polymer network and single-walled carbon nanotubes (SWCNTs) through host-guest interactions. The resulting materials show bulk electrical conductivity, proximity sensitivity, humidity sensitivity and are able to self-heal without external stimulus under ambient conditions rapidly. Furthermore, they also possess elasticity comparable to commercial rubbers.

pH-responsive polymer-drug conjugates as multifunctional micelles for cancer-drug delivery.

We developed a novel linear pH-sensitive conjugate methoxy poly(ethylene glycol)-4ß-aminopodophyllotoxin (mPEG-NPOD-I) by a covalently linked 4ß-aminopodophyllotoxin (NPOD) and PEG via imine bond, which was amphiphilic and self-assembled to micelles in an aqueous solution. The mPEG-NPOD-I micelles simultaneously served as an anticancer drug conjugate and as drug carriers. As a drug conjugate, mPEG-NPOD-I showed a significantly faster NPOD release at a mildly acidic pH of 5.0 and 4.0 than a physiological pH of 7.4. Notably, it was confirmed that this drug conjugate could efficiently deliver NPOD to the nuclei of the tumor cells and led to much more cytotoxic effects to A549, Hela, and HepG2 cancer cells than the parent NPOD. The half maximal inhibitory concentration (IC50) of mPEG-NPOD-I was about one order magnitude lower than that of the NPOD. In vivo, mPEG-NPOD-I reduced the size of the tumors significantly, and the biodistribution studies indicated that this drug conjugate could selectively accumulate in tumor tissues. As drug carriers, the mPEG-NPOD-I micelles encapsulated hydrophobic PTX with drug-loading efficiencies of 57% and drug-loading content of 16%. The loaded PTX also showed pH-triggered fast release behavior, and good additive cytotoxicity effect was observed for the PEG-NPOD-I/PTX. We are convinced that these multifunctional drug conjugate micelles have tremendous potential for targeted cancer therapy.

A Supramolecular Assembly of EGCG for Long-Term Treatment of Allergic Rhinitis.

Allergic rhinitis (AR) is a type-I hypersensitivity disease mediated by immunoglobulin E (IgE). Although antihistamines, glucocorticoids, leukotriene receptor antagonists, and other drugs are widely used to treat AR, the various adverse side effects of long-term use of these drugs should not be ignored. Therefore, more effective and safe natural alternative strategies are urgently needed. To this end, this study designed a nanosupramolecular delivery system composed of ß-cyclodextrin supramolecular polymer (PCD), thiolated chitosan (TCS), and natural polyphenol epigallocatechin gallate (EGCG) for intranasal topical continuous treatment of AR. The TCS/PCD@EGCG nanocarriers exhibited an excellent performance in terms of retention and permeability in the nasal mucosa and released the vast majority of EGCG responsively in the nasal microenvironment, thus resulting in the significantly high antibacterial and antioxidant capacities. According to the in vitro model, compared with free EGCG, TCS/PCD@EGCG inhibited mast cell activity and abnormal histamine secretion in a more long-term and sustained manner. According to the in vivo model, whether in the presence of continuous or intermittent administration, TCS/PCD@EGCG substantially inhibited the secretion of allergenic factors and inflammatory factors, mitigated the pathological changes of nasal mucosa, alleviated the symptoms of rhinitis in mice, and produced a satisfactory therapeutic effect on AR. In particular, the therapeutic effect of TCS/PCD@EGCG systems were even superior to that of budesonide during intermittent treatment. Therefore, the TCS/PCD@EGCG nanocarrier is a potential long-lasting antiallergic medicine for the treatment of AR.

Photoreversible polymer-surfactant micelles using the molecular recognition of α-cyclodextrin.

Photoreversible micelles were achieved by a combination of commercially available components sodium alginate (Alg), tetradecyltrimethylammonium bromide (TTAB), α-cyclodextrin (α-CD), and 4-(phenylazo)benzoic acid (PBA). Under visible light irradiation, α-CD interacted more favorably with PBA than with alkyl chains of TTAB. Therefore, polymer-surfactant micelles were formed by the self-assembly of Alg and TTAB through electrostatic attraction. After UV irradiation, micelles were disrupted because PBA in the cis form lost its ability to complex with α-CD, and then the latter was interacted with TTAB to prevent the association of alkyl chains of TTAB. On alternating irradiation of this quaternary system with UV and visible light, this reversible micellization process can be recycled many times.

Cyclodextrin-based microcapsules as bioreactors for ATP biosynthesis.

A biomimetic energy converter was fabricated via the assembly of CF0F1-ATPase on lipid-coated hollow nanocapsules composed of α-cyclodextrins/chitosan-graft-poly(ethylene glycol) methacrylate. Upon entrapped GOD into these capsules, the addition of glucose could trigger proton-motive force and then drive the rotation of ATPase to synthesize ATP.

Vesicular gold assemblies based on host-guest inclusion and its controllable release of doxorubicin.

We have developed a kind of gold nanoparticle (AuNP) in which polyethylene glycol (PEG) and poly(N-isopropylacrylamide) (PNIPAM) are attached on the surface of a gold nanocrystal through the host-guest inclusion between adamantane groups (ADA) and ß-cyclodextrin (ß-CD). The resulting AuNPs become amphiphilic in water above body temperature and self-assemble into vesicles. It is found that these vesicles can load doxorubicin (Dox) effectively. With a decrease in temperature, the PNIPAM shifted from hydrophobic to hydrophilic, causing Au vesicles to disassemble into stable small AuNPs, triggering the release of Dox. These hybrid vesicles, combining polymer functionality with the intriguing properties of AuNPs, can first release free Dox and AuNP/Dox at a site of a tumor through the application of either simple ice packs or deeply penetrating cryoprobes, then the AuNP/Dox can be taken in by tumor cells and destroy them like miniature munitions. Furthermore, these vesicles showed other therapeutic possibilities due to the presence of gold. We believe that the development of such multi-functional vesicles will provide new and therapeutically useful means for medical applications.

pH-Switchable macroscopic assembly through host-guest inclusion.

A novel pH-switchable macroscopic assembly is reported using alginate-based hydrogels functionalized with host (α-cyclodextrin, αCD) and guest (diethylenetriamine, DETA) moieties. Since the interaction of αCD and DETA is pH sensitive, the host hydrogel and guest hydrogel could adhere together when the pH is 11.5 and separate when the pH is 7.0. Furthermore, this pH-controlled adhesion and dissociation shows a good reversibility. The host and guest polymers have good biocompatibility; therefore, this pH-sensitive macroscopic assembly shows great potential in biotechnological and biomedical applications.

Redox- and glucose-induced shape-memory polymers.

A novel redox-induced shape-memory polymer (SMP) is prepared by crosslinking ß-cyclodextrin modified chitosan (ß-CD-CS) and ferrocene modified branched ethylene imine polymer (Fc-PEI). The resulting ß-CD-CS/Fc-PEI contains two crosslinks: reversible redox-sensitive ß-CD-Fc inclusion complexes serving as reversible phases, and covalent crosslinks serving as fixing phases. It is shown that this material can be processed into temporary shapes as needed in the reduced state and recovers its initial shape after oxidation. The recovery ratio and the fixity ratio are both above 70%. Furthermore, after entrapping glucose oxidase (GOD) in the system, the material shows a shape memory effect in response to glucose. The recovery ratio and the fixity ratio are also above 70%.

The expression levels of circulating miR-140-3p, miR-130a-3p, and miR-320b as diagnostic biomarkers in acute ischemic stroke.

Plasma miRNAs can characterize several diseases, including acute ischemic stroke (AIS), which is noninvasive and currently affordable in most laboratories worldwide. We aimed to demonstrate plasma miR-140-3p, miR-130a-3p, and miR-320b as diagnostic biomarkers in AIS.GSE110993 and GSE86291 datasets were analyzed to obtain plasma differentially expressed miRNAs between AIS and healthy control subjects (HCs). We further applied RT-qPCR for the validation in 85 AIS patients and 85 HCs. Receiver operating characteristic (ROC) curve were conducted to evaluate their diagnostic utility in AIS. Correlation was analyzed between DEmiRNAs and clinical and laboratory parameters, as well as inflammatory markers. The plasma levels of miR-140-3p, miR-130a-3p, and miR-320b were found to be consistently altered in both GSE110993 and GSE86291 datasets. In comparison to HCs, AIS patients at admission exhibited lower levels of miR-140-3p and miR-320b and higher level of miR-130a-3p in their plasma. The ROC analysis revealed that plasma miR-140-3p, miR-130a-3p, and miR-320b had area under the curve values of 0.790, 0.831, and 0.907, respectively. When combined, these miRNAs showed superior discriminatory power with a sensitivity of 91.76% and specificity of 95.29%. Plasma miR-140-3p and miR-320b negatively correlated glucose levels and inflammatory markers (IL-6, MMP-2, MMP-9, and VEGF) in AIS patients. Conversely, plasma miR-130a-3p levels were positively associated with glucose levels and these markers. Plasma miR-140-3p, miR-130a-3p, and miR-320b levels varied significantly among AIS patients with different NIHSS scores. Plasma miR-140-3p, miR-130a-3p, and miR-320b had high diagnostic value in AIS patients, which were correlated with inflammation and severity in stroke.

Poly ß-Cyclodextrin/Quaternary Ammoniated Chitosan Cryogel with a Porous Structure for Effective Hemostasis.

Uncontrolled bleeding is one of the most important causes threatening human health, but quick hemostasis remains a challenge. We prepared porous cryogels with poly ß-cyclodextrin (Pß-CD) and quaternary ammoniated chitosan (QCs). Pß-CD acts as a "water-grabbing agent" to assist QCs' ability to absorb and concentrate blood rapidly. The rat-tail amputation model and liver injury model exhibited that cryogels had excellent hemostatic performance. Moreover, cryogels showed good antibacterial activity and biocompatibility. Therefore, these cryogels can be used as potential hemostatic materials.

Double-Layer Hydrogel with Glucose-Activated Two-Stage ROS Regulating Properties for Programmed Diabetic Wound Healing.

Slow healing of wounds induces great pain in diabetic patients. However, developing new approaches to promote diabetic wound healing is still one of the toughest challenges in the medical field. Here, we constructed a new double-layer hydrogel to effectively regulate reactive oxygen species (ROS) on the wound and promote diabetic wound healing. The inner layer contains glucose oxidase (Gox), ferrocene-modified quaternary ammonium chitosan (Fc-QCs), and poly(ß-cyclodextrin) (Pß-CD), which is used to generate hydroxyl radicals (•OH) for antibacterial in the early stage of wound healing and collapses gradually. The outer layer is composed of gelatin and dopamine. In the later stage of wound healing, the outer layer contacts the skin, which is beneficial for ROS clearance on the wound. Antibacterial, ROS scavenging, and wound healing experiments have shown that the double-layer hydrogel possesses two-stage ROS regulating properties for programmed diabetic wound healing. In conclusion, it will be one of the most potential dressings for treating diabetic wounds in the future.

pH-induced shape-memory polymers.

A novel pH sensitive shape-memory polymer (SMP) is prepared by cross-linking the ß-cyclodextrin modified alginate (ß-CD-Alg) and diethylenetriamine modified alginate (DETA-Alg): The pH reversible ß-CD-DETA inclusion complexes serve as a reversible phase, and the cross-linked alginate chains serve as a fixing phase. It is shown that this material can be processed into temporary shape as we needs at pH 11.5 and recover to its initial shape at pH 7. The recovery ratio and the fixity ratio were 95.7 ± 0.9% and 94.8 ± 1.1%, respectively. Furthermore, this material showed good degradability and biocompatibility. Because the shape transition pH value is quite close to that of our body fluid and this pH triggered shape-memory effect is convenient and safe to use, this material has a high potential for medical application.

Bioinspired Ultra Tear-Resistant Elastomer with a Slidable Double-Network Structure.

Tear resistance is of vital importance in the fabrication and application of synthetic soft materials. However, the paradox of simultaneously improving the tearing energy and elasticity remains a huge challenge for conventional approaches. Here, inspired by the skin, we successfully constructed an extraordinary tear-resistant, superelastic elastomer by the introduction of nanosized polycyclodextrin into the elastomer network to form a slidable interpenetrate double network structure. The tearing energy of the SDEP elastomer is up to 274 KJ/m2, which is comparable to metals and alloys and increased more than 100 times compared with the chemically cross-linked elastomer. The fracture strain exceeded 3300%, which is hardly achieved by other materials with high tearing energy. This comprehensive improvement of antitearing and super elasticity property was achieved by (i) a slide ring effect to dissipate energy and blunt a crack tip; (ii) straightening and reorientation of the slidable double network to deflect the advancing of a crack tip; (iii) a double network sharing the load. These results provide a novel strategy to fabricate elastic, tear-resistant soft material, which may contribute to the practical application as tear-resistant flexible electronics and irregular-shaped stretchable devices.