Unrestricted molecular motions enable mild photothermy for recurrence-resistant FLASH antitumor radiotherapy.

Ultrahigh dose-rate (FLASH) radiotherapy is an emerging technology with excellent therapeutic effects and low biological toxicity. However, tumor recurrence largely impede the effectiveness of FLASH therapy. Overcoming tumor recurrence is crucial for practical FLASH applications. Here, we prepared an agarose-based thermosensitive hydrogel containing a mild photothermal agent (TPE-BBT) and a glutaminase inhibitor (CB-839). Within nanoparticles, TPE-BBT exhibits aggregation-induced emission peaked at 900 nm, while the unrestricted molecular motions endow TPE-BBT with a mild photothermy generation ability. The balanced photothermal effect and photoluminescence are ideal for phototheranostics. Upon 660-nm laser irradiation, the temperature-rising effect softens and hydrolyzes the hydrogel to release TPE-BBT and CB-839 into the tumor site for concurrent mild photothermal therapy and chemotherapy, jointly inhibiting homologous recombination repair of DNA. The enhanced FLASH radiotherapy efficiently kills the tumor tissue without recurrence and obvious systematic toxicity. This work deciphers the unrestricted molecular motions in bright organic fluorophores as a source of photothermy, and provides novel recurrence-resistant radiotherapy without adverse side effects.

Toughening Hydrogels by Forming Robust Hydrazide-Transition Metal Coordination Complexes.

Energy dissipation based on dynamic fracture of metal ligands is an effective way to toughen hydrogels for specific applications in biomedical and engineering fields. Exploration of new kinds of metal-ligand coordinates with robust bonding strength is crucial for the facile synthesis of tough gels. Here a hydrogel toughening strategy based on the formation of robust coordination complexes between the hydrazide ligands and zinc ions is reported. The resultant hydrogels exhibit high strength and toughness at room temperature. Their mechanical properties show temperature dependence due to the dynamic nature of coordination bonds. In addition, the amine group of hydrazides in the gel matrix provides a reactive site for Schiff's base reaction, enabling surface modification without influence on overall mechanical performances of the gel. The hydrazide ligands are easy to synthesize and can coordinate very well with several transition metals. Such a metal-ligand coordination should be suitable to develop tough soft materials with versatile applications.

Intrinsic Anti-Freezing and Unique Phosphorescence of Glassy Hydrogels with Ultrahigh Stiffness and Toughness at Low Temperatures.

Most hydrogels become frozen at subzero temperatures, leading to degraded properties and limited applications. Cryoprotectants are massively employed to improve anti-freezing property of hydrogels; however, there are accompanied disadvantages, such as varied networks, reduced mechanical properties, and the risk of cryoprotectant leakage in aqueous conditions. Reported here is the glassy hydrogel having intrinsic anti-freezing capacity and excellent optical and mechanical properties at ultra-low temperatures. Supramolecular hydrogel of poly(acrylamide-co-methacrylic acid) with moderate water content (≈50 wt.%) and dense hydrogen-bond associations is in a glassy state at room temperature. Since hydrogen bonds become strengthened as the temperature decreases, this gel becomes stronger and stiffer, yet still ductile, with Young's modulus of 900 MPa, tensile strength of 30 MPa, and breaking strain of 35% at -45 °C. This gel retains high transparency even in liquid nitrogen. It also exhibits unique phosphorescence due to presence of carbonyl clusters, which is further enhanced at subzero temperatures. Further investigations elucidate that the intrinsic anti-freezing property is related to a fact that most water molecules are tightly bound and confined in the glassy matrix and become non-freezable. This correlation, as validated in several systems, provides a roadmap to develop intrinsic anti-freezing hydrogels for widespread applications at extreme conditions.

Polymerization-Induced Crystallization of Dopant Molecules: An Efficient Strategy for Room-Temperature Phosphorescence of Hydrogels.

Conventional hydrogels such as polyacrylamide and polyacrylic acid ones seldom exhibit phosphorescences at ambient conditions, which limit their applications as optical materials. We propose and demonstrate here a facile strategy to afford these hydrogels with room-temperature phosphorescence by polymerization-induced crystallization of dopant molecules that results in segregation and confinement of the gel matrix with carbonyl groups and thus clusterization-induced phosphorescence. As a model system, crown ethers (CEs) are dissolved in an aqueous solution of concentrated acrylamide that greatly increases the solubility of CEs. During the polymerization process, CEs crystallize to form large spherulites in the polyacrylamide hydrogel. The crystallization arises from the drastically reduced solubility of CEs after the conversion of monomers to polymers during the gel synthesis. The resultant composite hydrogel with a water content of 67 wt % exhibits extraordinary phosphorescence behavior yet maintains good stretchability and resilience. We found that the partial gel matrix is squeezed and confined by in situ-formed crystals, leading to carbonyl clusters and thus phosphorescence emission. The composite gel shows green phosphorescence with an emission peak at 512 nm and a lifetime of 342 ms. The afterglow emission is detectable by the naked eye for several seconds. This strategy has good universality, as validated in other hydrogels with different polymeric matrices and dopant molecules. The development of hydrogels with good mechanical and phosphorescent properties should merit the design of multifunctional soft machines with applications in biomedical and engineering fields.

Paper without a Trail: Time-Dependent Encryption using Pillar[5]arene-Based Host-Guest Invisible Ink.

A stimuli-responsive invisible ink for time-dependent encryption of information is reported. Consisting of a pillar[5]arene-based supramolecular network grafted with spiropyran moieties, these materials display time-dependent photochromic behavior with tailorable fading rates. Ultraviolet (UV) light results in isomerization of the colorless spiropyran to the corresponding colored merocyanine, while visible light or heat causes the reverse isomerization with a rate that is dependent on the density of host-guest crosslinks. The kinetics of discoloration are a function of merocyanine aggregation, which becomes more pronounced as the host-guest crosslink density is increased, leading to a reduced conversion rate and slower time-dependent fading. The degree of crosslinking, and hence the fading rate, may be modulated via the addition of unbound pillar[5]arene host or nitrile guest as competitors. Time-dependent information encryption is enabled by combining selective placement of host and guest competitors and UV patterning. UV patterning provides an initially "false" image that does not reveal the desired information, and it is only after a given time that the encrypted data appears. This work provides a unique approach to enhance the security of information storage associated with offline portable data encryption.

Ultrastiff Hydrogels Prepared by Schiff's Base Reaction of Bis(p-Formylphenyl) Sebacate and Pillar[5]arene Appended with Multiple Hydrazides.

Herein a facile method is reported to prepare polymer gels based on the formation of acylhydrazone bond under mild conditions. A pillar[5]arene derivative appended with ten hydrazide groups provides multiple sites for the reaction with the aldehyde groups of bis(p-formylphenyl) sebacate in the presence of a small amount of HCl as the catalyst in dimethyl sulfoxide (DMSO), producing transparent polymer organogels. The mechanical properties of gels can be easily tuned by the molar ratio of the reactant compounds. After solvent exchange from DMSO to water, translucent polymer hydrogels with dramatically enhanced strength and stiffness are obtained. The tensile breaking stress and Young's modulus of hydrogels are 20-60 and 1.2-2.7 MPa, respectively, 100 and 20 times those of the corresponding organogels. These robust hydrogels with ultrahigh stiffness should find applications such as in load-bearing artificial organs. This work should merit designing functional materials using other macrocycles.