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Locoregional recurrence of breast cancer after tumor resection represents several clinical challenges. Here, we demonstrate that co-delivery of chemotherapy and thermotherapeutic agents by a magnetic supramolecular hydrogel (MSH) following tumor resection prevents tumor recurrence in a breast cancer mouse model. The self-assembled MSH was designed through the partial inclusion complexation associated with the threading of α-CD on the copolymer moieties on the surface of the PEGylated iron oxide (Fe 3 O 4 ) nanoparticles, which enables shear-thinning injection and controllable thermoreversible gel-sol transition. MSH was injected to the postoperative wound uniformly, which became mobile and perfect match with irregular cavity without blind angle due to the magnetocaloric gel-sol transition when exposed to alternating current magnetic field (ACMF). The magnetic nanoparticle-mediated induction heat during the gel-sol transition process caused the triggered release of dual-encapsulated chemotherapeutic drugs and provided an effect of thermally induced cell damage. The hierarchical structure of the MSH ensured that both hydrophobic and hydrophilic drugs can be loaded and consecutively delivered with different release curves. The hydrogel nanocomposite might provide a potential locally therapeutic approach for the precise treatment of locoregional recurrence of cancer., Statement of Significance: Tumor recurrence after resection represents several clinical challenges. In this study, we prepared shear-thinning injectable magnetic supramolecular hydrogel (MSH) and demonstrated their therapeutic applications in preventing the post-operative recurrence of breast cancer with facile synthesis and minimally invasive implantation in vivo. MSH was injected to the postoperative wound uniformly, which become mobile and perfect match with irregular cavity without blind angle through magnetocaloric gel-sol transition when exposed to ACMF. The magnetic nanoparticles mediated induction heat during the gel-sol transition process caused the triggered release of dual-encapsulated chemotherapeutic drugs as well as thermally induced cell damage. This study demonstrates that MSH with the controlled administration of combined thermo-chemotherapy exhibit great superiority in terms of preventing post-operation cancer relapse., (Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The development of codelivery systems for combination therapy that can load different drugs in a single carrier and precisely deliver payloads (ratio and administration time) via programmable administration has proven to be challenging. By taking advantage of the increased dimension or space from particle self-assembly approach, we have developed a prodrug-based cascade self-assembly strategy to construct a supramolecular hydrogel that can load different drugs in stages yet temporally/spatially release drugs by cascade disassembly of supramolecular hydrogel under different microenvironments. The cascade self-assembly mechanism has been investigated in detail by morphology evolution of prodrug micelles. Using tumor cell uptake, cytotoxicity assay, and a tumor-bearing animal model, the effectiveness of the prodrug micelle-based cascade self-assembly system was studied, such as loading, controlling the drug ratio, and the administration time for possible therapeutic applications. These studies fully demonstrate the proof of concept and open up an attractive new way to construct multidrug-loaded carriers for combination therapy.

The low bioavailability exhibits by conventional ocular formulation owing to rapid precorneal clearance and lower corneal permeability can be overcame by the application of the gelling system. In the present study, a prodrug supramolecular hydrogel derived from succinated dexamethasone (Dex-SA) was fabricated using a pH hydrolytic strategy and explored as a "self-delivery" system for ophthalmic drugs. The self-assembled Dex-SA supramolecular hydrogel exhibited a typical nano-fibrous microstructure and was thixotropic. Both dexamethasone (Dex) and Dex-SA prodrug sustainably released from Dex-SA supramolecular hydrogel in a period of 120 h in vitro release study, and the initial pH value of hydrogel significantly influence on the release ratio of Dex/Dex-SA. Furthermore, the lyophilized Dex-SA supramolecular hydrogel displayed long-term stability without causing any apparent hydrolysis of Dex-SA at -20 °C over 30 day and quickly re-formed a hydrogel after dissolving into aqueous solution. The formed Dex-SA supramolecular hydrogel had lower cytotoxicity than Dex at drug concentration up to 2.5 mM, and exhibited a comparable anti-inflammatory efficacy to a Dex sodium phosphate (Dexp) aqueous solution in lipopolysaccharide-activated RAW264.7 macrophages. Topical instillation of the Dex-SA supramolecular hydrogel showed excellent intraocular biocompatibility and it was not an irritant in rabbit eyes. More importantly, the Dex-SA supramolecular hydrogel provided a prolonged precorneal retention and significantly enhanced the ocular bioavailability over Dexp aqueous solution after topical instillation. Overall, this work illustrates an effective approach for the development of prodrug supramolecular hydrogels to extend the precorneal retention and enhance ocular bioavailability of drugs after topical instillation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Supramolecular hydrogels (SHGs) built from inclusion complex of macrocyclic compound α-cyclodextrin (α-CD) and poly(ethylene glycol) (PEG) have attracted much interest due to their excellent biocompatibility and great potential for biomedical applications. In this work, the hydrogen bond of nucleic acid was introduced into the above-mentioned SHG by syntheses of nucleobase guanine/cytosine (G/C)-terminated PEG (G-PEG-G/C-PEG-C). The base-pairing interaction between G and C as an additional network junction effectively enhanced storage moduli (G's) of the hydrogels. Moreover, the prepared hydrogels exhibited excellent cytocompatibility and property for controlled drug release, outlining the potential of thermo-sensitive construct for biomedical applications, such as local chemotherapy of cancers., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Enzyme-instructed self-assembly (EISA) offers a facile approach to explore the supramolecular assemblies of small molecules in cellular milieu for a variety of biomedical applications. One of the commonly used enzymes is phosphatase, but the study of the substrates of phosphatases mainly focuses on the phosphotyrosine containing peptides. In this work, we examine the EISA of phosphoserine containing small peptides for the first time by designing and synthesizing a series of precursors containing only phosphoserine or both phosphoserine and phosphotyrosine. Conjugating a phosphoserine to the C-terminal of a well-established self-assembling peptide backbone, (naphthalene-2-ly)-acetyl-diphenylalanine (NapFF), affords a novel hydrogelation precursor for EISA. The incorporation of phosphotyrosine, another substrate of phosphatase, into the resulting precursor, provides one more enzymatic trigger on a single molecule, and meanwhile increases the precursors' propensity to aggregate after being fully dephosphorylated. Exchanging the positions of phosphorylated serine and tyrosine in the peptide backbone provides insights on how the specific molecular structures influence self-assembling behaviors of small peptides and the subsequent cellular responses. Moreover, the utilization of D-amino acids largely enhances the biostability of the peptides, thus providing a unique soft material for potential biomedical applications.

A generally applicable strategy to obtain mechanically robust hydrogels for the incorporation and containment of functional reporter bacteria for the microarray and microparticle-based detection and signaling of N-acyl homoserine lactone autoinducers (3OC 12 HSL) at relevant concentrations is reported. For reinforcing hydrogels of 1,4-bi(phenylalanine-diglycol)-benzene (PDB), a hybrid hydrogel is formed by the combination of PDB self-assembly with Ca 2+ mediated alginate crosslinking. The different assembly mechanisms are shown not to interfere with each other and despite the more than four-fold increased moduli of the hydrogels, diffusion of autoinducers into the gels remains efficient and Escherichia coli pLuxR-green fluorescent protein (GFP) reporter bacteria are proliferating. Templating affords reporter bacteria-loaded hydrogels with controllable shape and size. Upon exposure to 3OC 12 HSL, the embedded bacteria exhibit an up to 12 ± 3 times increase in fluorescence intensity due to autoinducer-triggered GFP expression. This approach can serve as a potentially generally applicable strategy to sensitively detect bacteria via their secreted autoinducers., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We report here on the covalent conversion of the anti-inflammatory agent ketoprofen into self-assembling prodrugs that enable the effective purification of ketoprofen enantiomers, the improved selectivity and potency of ketoprofen, as well as the formation of one-component drug-bearing supramolecular hydrogels. We found that the ketoprofen hydrogelator could exhibit much-enhanced selectivity for cyclooxygenase 2 (COX-2) over COX-1, reduce the concentration of inflammatory cytokines (IL-1 and TNFα), and induce apoptosis in fibroblast-like synoviocytes while maintaining biocompatibility with healthy chondrocytes. In addition, these anti-inflammatory agent-containing hydrogels demonstrated the ability to retain the therapeutic within a joint cavity after intra-articular injection, exhibiting a slow, steady release into the plasma. We believe that upon further optimization these drug-based injectable supramolecular hydrogels could provide the basis for a local treatment strategy for rheumatoid arthritis and similar conditions., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Poor, nontunable mechanical properties as well as finite shape memory performance pose a barrier to shape memory hydrogels to realize practical applications. Here, a new shape memory hydrogel with tunable mechanical properties and multishape memory effect was presented. Three programmable reversible systems including PBA-diol ester bonds, AAc-Fe 3+ , and coil-helix transition of agar were applied to memorize temporary shapes and endow the hydrogel with outstanding multishape memory functionalities. Moreover, through changing the cross-linking densities, the mechanical properties of the as-prepared hydrogel can be adjusted.

The article discusses the formation of supramolecular hydrogels based on diacetylene-bridge phenylamine. Topics discussed include the use of fluorimetry to study the fluorescence properties of the hydrogels, the evaluation of the gelation properties of the hydrogels using different organic solvents, and the effect of restriction of molecular rotation with hydrogen bonding interaction on the luminescence properties of one of the hydrogel.

Pectin is an anionic, water-soluble polymer predominantly consisting of covalently 1,4-linked α-d-galacturonic acid units. This naturally occurring, renewable and biodegradable polymer is underutilized in polymer science due to its insolubility in organic solvents, which renders conventional polymerization methods impractical. To circumvent this problem, cerium-initiated radical polymerization was utilized to graft methoxy-poly(ethylene glycol) methacrylate (mPEGMA) onto pectin in water. The copolymers were characterized by ¹H nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR) spectroscopy and thermogravimetric analysis (TGA), and used in the formation of supramolecular hydrogels through the addition of α-cyclodextrin (α-CD) to induce crosslinking. These hydrogels possessed thixotropic properties; shear-thinning to liquid upon agitation but settling into gels at rest. In contrast to most of the other hydrogels produced through the use of poly(ethylene glycol) (PEG)-grafted polymers, the pectin-PEGMA/α-CD hydrogels were unaffected by temperature changes.

Bacteria contamination in drinking water and medical products can cause severe health problems. However, currently available sterilization methods, mainly based on the size-exclusion mechanism, are typically slow and require the entire contaminated water to pass through the filter. Here, we present an electroresponsive hydrogel based approach for bacteria adsorption and removal. We successfully engineered a series of graphene oxide hydrogels using redox-active ruthenium complexes as noncovalent cross-linkers. The resulting hydrogels can reversibly switch their physical properties in response to the applied electric field along with the changes of oxidation states of the ruthenium ions. The hydrogels display strong bacteria adsorbing capability. A hydrogel of 1 cm(3) can adsorb a maximum of 1 × 10(8) E. coli. The adsorbed bacteria in the hydrogels can then be inactivated by a high voltage electric pulse and removed from the hydrogels subsequently. Owing to the high bacteria removal rate, reusability, and low production cost, these hydrogels represent promising candidates for the emergent sterilization of medical products or large-scale purification of drinking water.

Aerogels with low density and high porosity show outstanding properties such as large surface area and low thermal and acoustic conductivity. However, great challenges remain to convert hydrophilic polymer based hydrogels to corresponding aerogels. Here, we report a structurally new type of aerogels, supramolecular aerogels (SMAs), derived from supramolecular hydrogels formed by self-assembling of poly(ethylene glycol) and α-/γ-cyclodextrin. The SMAs posses a characteristic binary crystallized nanosheet structure due to their supramolecular cross-linking nature, and their specific surface areas and nanosheet structures are tunable. Furthermore, we demonstrated application of the aerogels as solid-solid phase change materials with tunable latent heat, reversible melting-crystallization cycle while keeping the microstructure of the SMAs unchanged.

A multiresponsive hydrogel system coassembled from phenylalanine derivative gelator (LPF2) and azobenzene (Azo) derivative (PPI) is constructed, which can respond to temperature, pH, host-guest interaction, and photoirradiation. A set of techniques including circular dichroism, Fourier transform infrared spectroscopy, (1)H NMR, and X-ray powder diffraction confirm that the hydrogel is formed through hydrogen bonds between amide moieties/pyridine and carbonyl groups, enduing the coassembled hydrogel with multiresponsive properties that make it possible to control cell encapsulation and release in three-dimensional environments under multistimulus, for example, UV irradiation. This study brings a novel approach to develop multistimuli-responsive hydrogels by coassembly of various responsive components for biomedical interest, for example, the controlled delivery of various therapeutic biological agents.

Supramolecular hydrogels (SMHs) are three-dimensional networks filled with a large amount of water. The crosslinking force in the 3D network is always constructed by relatively weak and dynamic non-covalent interactions, and thus SMHs usually possess extremely high susceptibility to external environment and can show extraordinary stimuli-responsive, self-healing or other attractive properties. However, the overall crosslinking force in hydrogel networks is difficult to flexibly modulate, and this leads to limited functions of the SMHs. In this regard, hierarchical hydrogen bonds, that is, the mixture of relatively strong and relatively weak hydrogen bonds, are used herein as crosslinking force for the hydrogel preparation. The ratio of strong and weak hydrogen bonds can be finely tuned to tailor the properties of resultant gels. Thus, by delicate manipulation of the overall crosslinking force in the system, a hydrogel with multiple (thermal, pH and NIR light) responsiveness, autonomous self-healing property and interesting temperature dependent, reversible adhesion behavior is obtained. This kind of hierarchical hydrogen bond manipulation is proved to be a general method for multiple-functionality hydrogel preparation, and the resultant material shows potential for a range of applications., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Supramolecular materials with noncovalent bonds have attracted much attention due to their exclusive properties differentiating them from materials formed solely by covalent bonds. Especially interesting are rotor molecules of topological complexes that shuttle along a polymer chain. The shuttling of these molecules should greatly improve the tension strength. Our research employs cyclodextrin (CD) as a host molecule, because CD effectively forms polyrotaxanes with polymers. Herein we report the formation of supramolecular hydrogels with an α-CD dimer (α,α-CD dimer) as a topological linker molecule, and a viologen polymer (VP) as the polymer chain. The supramolecular hydrogel of α,α-CD dimer/VP forms a self-standing gel, which does not relax (G' > G'') in the frequency range 0.01-10 rad·s(-1). On the other hand, the supramolecular hydrogel decomposes upon addition of bispyridyl decamethylene (PyC(10)Py) as a competitive guest. Moreover, the β-CD dimer (β,β-CD dimer) with VP does not form a supramolecular hydrogel, indicating that complexation between the C(10) unit of VP and the α-CD unit of the α,α-CD dimer plays an important role in the formation of supramolecular hydrogels.