Multi-Responsive Peptide-Based Ultrathin Nanosheets Prepared by a Horizontal Monolayer Assembly.

In this study, peptide-based self-assembled nanosheets with a thickness of approximately 1 nm were prepared using a hierarchical covalent physical fabrication strategy. The covalent alternating polymerization of helical peptide E3 with an azobenzene (AZO) structure yielded copolymers CoP(E3-AZO), which physically self-assembled into ultrathin nanosheets in an unanticipated two-dimensional horizontal monolayer arrangement. This special monolayer arrangement enabled the thickness of the nanosheets to be equal to the cross-sectional diameter of a single linear copolymer, which is a rare phenomenon. Molecular dynamics simulations suggested that the synergistic effect of multiple molecular interactions drives the self-assembly of CoP(E3-AZO) into nanosheets and that various methods, including phototreatment, pH adjustment, the addition of additives, and introduction of cosolvents, can alter the molecular interactions and modulate the self-assembly of CoP(E3-AZO), yielding diverse nanostructures. Remarkably, the ultrathin nanosheets selectively inhibited cancer cells at certain concentrations.

Multi-Responsive Molecular Encapsulation and Release Based on Hydrogen-Bonded Azo-Macrocycle.

Research on stimuli-responsive host-guest systems is at the cutting edge of supramolecular chemistry, owing to their numerous potential applications such as catalysis, molecular machines, and drug delivery. Herein, we present a multi-responsive host-guest system comprising azo-macrocycle 1 and 4,4'-bipyridinium salt G1 for pH-, photo-, and cation- responsiveness. Previously, we reported a novel hydrogen-bonded azo-macrocycle 1. The size of this host can be controlled through light-induced E↔Z photo-isomerization of the constituent azo-benzenes. The host is found in this work to be capable of forming stable complexes with bipyridinium/pyridinium salts, and implementing guest capture and release with G1 under light in a controlled manner. The binding and release of the guest in the complexes can also be easily controlled reversibly by using acid and base. Moreover, the cation competition-induced dissociation of the complex 1a2⊃G1 is achieved. These findings are expected to be useful in regulating encapsulation for sophisticated supramolecular systems.

Wires with Continuous Sabal Leaf-Patterned Micropores Constructed by Freeze Printing for a Wearable Sensor Responsible to Multiple Deformations.

The design of porous structure in wearable sensors is very important for the detection of mechanical signals. However, it remains challenging to construct a porous structure capable of detecting all kinds of mechanical signals. Here, round wire with long-range orientated micropores (RW-LOM) is fabricated by a newly established freeze printing technique and constructed into a wearable sensor by the incorporation of carbon nanotubes and polydimethylsiloxane. The Sabal leaf-like lamellar structure in RW-LOM is realized and can be tuned by the proper coordination of slurry concentration and the printing parameters. The fine structures in RW-LOM allow the wearable sensor to detect compression, stretching, twisting, and bending with a high sensitivity, stability, and broad detecting range. This work not only provides a wearable sensor with high stability and high sensitivity but also establishes a technique to construct porous wires that could find applications in the fields like intelligent industry and healthcare.

Multiresponsive Polymer Nanocomposite Liquid Crystals Having Heterogeneous Phase Transitions for Battery-Free Temperature Maintenance Indicators.

Multiresponsive functional materials that respond to more than one external stimulus are promising for novel photonic, electronic, and biomedical applications. However, the design or synthesis of new multiresponsive materials is challenging. Here, this work reports a facile method to prepare a multiresponsive colloidal material by mixing a liquid-crystalline 2D nanocolloid and a functional polymer colloid. For this purpose, electrically sensitive exfoliated α-ZrP 2D nanocolloids and thermosensitive block copolymer colloids that are dispersed well in water are mixed. In the liquid-crystalline nanocomposite, nematic, antinematic, or isotropic assemblies of α-ZrP, nanoparticles can be electrically and selectively obtained by applying electric fields with different frequencies; furthermore, their rheology is thermally and reversibly controlled through thesol-gel-sol transition. The nanocomposite exhibits a solid gel phase within a predesigned gel temperature range and a liquid sol phase outside this range. These properties facilitate the design of a simple display device in which information can be electrically written and thermally stabilized or erased, and using the device, a battery-free temperature maintenance indication function is demonstrated. The proposed polymer nanocomposite method can enrich the physical properties of 2D nanocolloidal liquid crystals and create new opportunities for eco-friendly, reusable, battery-free electro-optical devices.

Recent Advances in Multiresponsive Flexible Sensors towards E-skin: A Delicate Design for Versatile Sensing.

Multiresponsive flexile sensors with strain, temperature, humidity, and other sensing abilities serving as real electronic skin (e-skin) have manifested great application potential in flexible electronics, artificial intelligence (AI), and Internet of Things (IoT). Although numerous flexible sensors with sole sensing function have already been reported since the concept of e-skin, that mimics the sensing features of human skin, was proposed about a decade ago, the ones with more sensing capacities as new emergences are urgently demanded. However, highly integrated and highly sensitive flexible sensors with multiresponsive functions are becoming a big thrust for the detection of human body motions, physiological signals (e.g., skin temperature, blood pressure, electrocardiograms (ECG), electromyograms (EMG), sweat, etc.) and environmental stimuli (e.g., light, magnetic field, volatile organic compounds (VOCs)), which are vital to real-time and all-round human health monitoring and management. Herein, this review summarizes the design, manufacturing, and application of multiresponsive flexible sensors and presents the future challenges of fabricating these sensors for the next-generation e-skin and wearable electronics.

Cascaded Multiresponsive Self-Assembled 19F MRI Nanoprobes with Redox-Triggered Activation and NIR-Induced Amplification.

Molecular probes featuring promising capabilities including specific targeting, high signal-to-noise ratio, and in situ visualization of deep tissues are in great demand for tumor diagnosis and therapy. 19F magnetic resonance imaging (MRI) techniques incorporating stimuli-responsive probes are anticipated to be highly beneficial for specific detection and imaging of tumors because of negligible background and deep tissue penetration. Herein, we report a cascaded multiresponsive self-assembled nanoprobe, which enables sequential redox-triggered and near-infrared (NIR) irradiation-induced 19F MR signal activation/amplification for sensing and imaging. Specifically, we designed and synthesized a cascaded multiresponsive 19F-bearing nanoprobe based on the self-assembly of amphiphilic redox-responsive 19F-containing polymers and NIR-absorbing indocyanine green (ICG) molecules. It could realize the activation of 19F signals in the reducing tumor microenvironment and subsequent signal amplification via the photothermal process. This stepwise two-stage activation/amplification of 19F signals was validated by 19F NMR and MRI both in vitro and in vivo. The multiresponsive 19F nanoprobes capable of cascaded 19F signal activation/amplification and photothermal effect exertion can provide accurate sensing and imaging of tumors.

Discrete Heteropolynuclear Yb/Er Assemblies: Switching on Molecular Upconversion Under Mild Conditions.

The salts {[Ln2 Ln*(Hhmq)3 (OAc)3 (hfac)2 ]+ [Ln*(hfac)3 (OAc)(MeOH)]- } (Hhmq=2-methanolquinolin-8-oxide, hfac=hexafluoroacetylacetonate; Ln, Ln*=Er, Gd, Yb) feature a discrete heteronuclear cation consisting of two types of lanthanide atoms. The quinolinoxy O-atom serves as a µ2 -bridge to two Ln atoms and as a µ3 -bridge to all three atoms, with metal⋅⋅⋅metal distances being around 3.7 Å. For 1 ([Yb2 Er]+ ), near-infrared downshifted luminescence is switched to competitive upconversion luminescence upon irradiation by a 980 nm laser under an extremely low excitation power (0.288 W cm-2 ) through introduction of fluoride ions. The stability of 1 after addition of fluoride was confirmed by powder X-ray diffraction and multistage mass spectrometry, associated with the 1 H NMR of 6 ([La2 Eu]+ ). More importantly, the at least 20-fold enhancement of the quantum yield in non-deuterated solvents at room temperature under low power densities (2 W cm-2 ) is the highest among the few molecular examples reported.

Self-Assembly of Surface-Acylated Cellulose Nanowhiskers and Graphene Oxide for Multiresponsive Janus-Like Films with Time-Dependent Dry-State Structures.

For the first time Janus-like films of surface-acylated cellulose nanowhiskers (CNWs) with or without graphene oxide (GO) via one-step evaporation-driven self-assembly process are reported, which have reconstructible time-dependent micro-/nanostructures and asymmetric wettability. The heterogeneous aggregation of CNWs on rough Teflon substrates favors the formation of uniform films, leading to hydrophobic smooth bottom surface. The homogeneous nucleation of residual CNWs in bulk suspensions promotes the growth of patchy microspheres with an average diameter of 22.7 ± 2.1 µm, which precipitate on the top surface leading to enhanced hydrophobicity. These patchy microspheres are thermoresponsive and vanish after heating at 60 °C within 1 min, while they are reconstructed at room temperature with time-dependent evolving micro-/nanostructures in dry state within 2 d. The thermoresponsive transition of patchy microparticles leads to accompanied switchable change between transparency and opacity of Janus-like films. Furthermore, the incorporation of GO generates more patchy microspheres with an average diameter of 13.5 ± 1.3 µm on the top surface of hybrid Janus-like films. Different distributions of CNWs and GO in Janus-like films and the solvent-responsive self-assembled patchy microparticles of CNWs facilitate their reversible actuation by showing fast curling in THF within 6 s and flattening in water for at least 25 cycles.

A Bis-Acridinium Macrocycle as Multi-Responsive Receptor and Selective Phase-Transfer Agent of Perylene.

A bis-acridinium cyclophane incorporating switchable acridinium moieties linked by a 3,5-dipyridylanisole spacer was studied as a multi-responsive host for polycyclic aromatic hydrocarbon guests. Complexation of perylene was shown to be the most effective and was characterized in particular by a charge-transfer band as signal output. Effective catch and release of the guest was triggered by both chemical (proton/hydroxide) and redox stimuli. Moreover, the dicationic host was also easily switched between organic and perfluorocarbon phases for applications related to the enrichment of perylene from a mixture of polycyclic aromatic hydrocarbons.

Influence of Chain Architecture on Nanopore Accessibility in Polyelectrolyte Block-Co-Oligomer Functionalized Mesopores.

Functionalized ordered mesoporous silica materials are commonly investigated for applications such as drug release, sensing, and separation processes. Although, various homopolymer functionalized responsive mesopores are reported, little focus has been put on copolymers in mesopores. Mesoporous silica films are functionalized with responsive and orthogonally charged block-co-oligomers. Responsive 2-dimethylamino)ethyl methacrylate)-block-2-(methacryloyloxy)ethyl phosphate (DMAEMA-b-MEP) block-co-oligomers are introduced into mesoporous films using controlled photoiniferter initiated polymerization. This approach allows a very flexible charge composition design. The obtained block-co-oligomer functionalized mesopores show a complex gating behavior indicating a strong interplay between the different blocks emphasizing the strong influence of charge distribution inside mesopores on ionic pore accessibility. For example, in contrast to mesopores functionalized with zwitterionic polymers, DMAEMA-b-MEP block-co-oligomer functionalized mesopores, containing two oppositely charged blocks, do not show bipolar ion exclusion, demonstrating the influence of the chain architecture on mesopore accessibility. Furthermore, ligand binding-based selective gating is strongly influenced by this chain architecture as demonstrated by an expansion of pore accessibility states for block-co-oligomer functionalized mesopores as compared to the individual polyelectrolyte functionalization for calcium induced gating.

"Breathing" CO2 -, O2 -, and Light-Responsive Vesicles from a Triblock Copolymer for Rate-Tunable Controlled Release.

A well-defined amphiphilic triblock copolymer, poly[(ethylene glycol)methyl ether]-block-poly(N,N-dimethylamino ethyl methacrylate-co-2,2,2-trifluoroethyl methacrylate)-block-poly(4-(4-methoxy-phenylazo)phenoxy methacrylate) (PEG-b-P(DMAEMA-co-TFEMA)-b-PMEPPMA), is successfully synthesized by stepwise atom transfer radical polymerization. Owing to its amphiphilic nature, PEG-b-P(DMAEMA-co-TFEMA)-b-PMEPPMA can self-assemble into vesicles in aqueous solution and exhibits a reversible triple-responsive behavior toward CO2 , O2 , and light stimuli. More importantly, such vesicles can exhibit a controlled "breathing" behavior via external stimuli due to their suitable chemical structure and stimuli responsiveness. Consequently, these vesicles can be employed as nanocarriers for rate-tunable controlled release via adjustment of their membrane permeability by a single stimulus or various stimuli combinations.

Fluorescent multi-responsive cross-linked P(N-isopropylacrylamide)-based nanocomposites for cisplatin delivery.

Magnetic, pH and temperature-sensitive, poly(N-isopropylacrylamide) (PNIPAM)-based nanocomposites with fluorescent properties were synthesized by free radical copolymerization-cross linking of NIPAM, N,N-dimethylaminoethyl methacrylate (DMAEMA) and 4-acrylamidofluorescein (AFA). The model anti-cancer drug, cisplatin (CDDP), was loaded into the resulted nanogel. For the production of CDDP-loaded nanocomposite, Fe3O4 magnetic nanoparticles (MNPs) and CDDP were loaded into the nanogel. Field-emission scanning electron microscopy (FE-SEM) indicated that the size of nanogel and CDDP-loaded nanocomposite were about 90 and 160 nm, respectively. The encapsulation efficiency of CCDP was found up to 65%. The loaded CCDP showed sustained thermal and pH-responsive drug release. A high level of drug release was observed under the conditions of low pH and high temperature. The lower critical solution temperature (LCST) of synthesized nanogel was about 40 °C. CDDP-loaded nanocomposite showed a volume phase transition from 282 to 128 nm at its LCST. Accordingly, in this study, the synthesized nanocomposite can be employed as a stimuli-responsive anti-cancer drug delivery system and the pH and temperature of solution have the potential to monitor the drug release.

Superparamagnetic Reduction/pH/Temperature Multistimuli-Responsive Nanoparticles for Targeted and Controlled Antitumor Drug Delivery.

Multistimuli-responsive polymeric nanoparticles with core-shell architecture were prepared by coating superparamagnetic Fe3O4 nanoparticle cores with reduction/pH dual-responsive poly(methacrylic acid) (PMAA) as shells and thermal-responsive poly(N-isopropylacrylamide) (PNIPAM) as a "gatekeeper" on the surface via two-stage distillation precipitation polymerization. The Fe3O4@PMAA nanoparticles were synthesized using N,N-bis(acryloyl)cystamine (BACy) as cross-linker which would be easily biodegradable in the presence of dithiothreitol (DTT) or glutathione (GSH). The cumulative release profile was investigated under different conditions, such as media pH, reductive agents, and temperature, with doxorubicin hydrochloride (DOX) as a model anticancer drug. They showed a low leakage of DOX at pH 7.4 (less than 11% in 24 h), while the release significantly accelerated at pH 5.0 and 10 mM GSH (over 60% in 5 h), realizing the "triggered release" of drug in the targeted tissues. The nanoparticles exhibited excellent biocompatibility while the DOX-loaded nanoparticles showed great promise of antitumor efficacy as free DOX by the MTT assay and CLSM analysis. The results suggest that the novel biodegradable nanoparticles with high drug loading capacity and multiresponsive controlled release capability could serve as an excellent gene/drug delivery system candidate for cancer therapy.

Multi-responsive photo- and chemo-electrical single-molecule switches.

Incorporating molecular switches as the active components in nanoscale electrical devices represents a current challenge in molecular electronics. It demands key requirements that need to be simultaneously addressed including fast responses to external stimuli and stable attachment of the molecules to the electrodes while mimicking the operation of conventional electronic components. Here, we report a single-molecule switching device that responds electrically to optical and chemical stimuli. A light pointer or a chemical signal can rapidly and reversibly induce the isomerization of bifunctional spiropyran derivatives in the bulk reservoir and, consequently, switch the electrical conductivity of the single-molecule device between a low and a high level. The spiropyran derivatives employed are chemically functionalized such that they can respond in fast but practical time scales. The unique multistimuli response and the synthetic versatility to control the switching schemes of this single-molecule device suggest spiropyran derivatives as key candidates for molecular circuitry.

Optical devices constructed from multiresponsive microgels.

Novel multiresponsive microgels based on poly(N-isopropylacrylamide) were synthesized to contain triphenylmethane leucohydroxide, and used to construct etalons. The optical properties of the resultant etalons were investigated, and their response to ultraviolet and visible irradiation, solution pH changes, and the presence of a mimic of the nerve agent Tabun characterized. We clearly show that the optical properties of the device depended dramatically on these stimuli. This investigation illustrates the versatility of the microgel-based etalon structure, and showcases the clear utility of such devices for remote actuation, color tunable optics, sensing, and potential remotely triggered drug delivery applications.

Bioinspired Multistimuli-Induced Synergistic Changes in Color and Shape of Hydrogel and Actuator Based on Fluorescent Microgels.

Fluorescent hydrogels have emerged as one of the most promising candidates for developing biomimetic materials and artificial intelligence owing to their unique fluorescence and responsive properties. However, it is still challenging to fabricate hydrogel that exhibits synergistic changes in fluorescence color and shape in response to multistimulus via a simple method. Herein, blue- and orange-emitting fluorescent microgels (MGs) both are designed and synthesized with pH-, thermal-, and cationic-sensitivity via one-step polymerization, respectively. The two fluorescent MGs are incorporated into transparent doubly crosslinked microgel (DX MG) hydrogels with a preset ratio. The DX MG hydrogels can tune the fluorescent color accompanied by size variation via subjecting to external multistimulus. Thus, DX MG hydrogels can be exploited for multiresponsive fluorescent bilayer actuators. The actuators can undergo complex shape deformation and color changes. Inspired by natural organisms, an artificial morning glory with color and size changes are showcased in response to buffer solutions of different pH values. Besides, an intelligent skin hydrogel, imitating natural calotes versicolor, by assembling four layers of DX MG with different ratios of MGs, is tailored. This work serves as an inspiration for the design and fabrication of novel biomimetic smart materials with synergistic functions.

Quantum-Confined-Superfluidics-Enabled Multiresponsive MXene-Based Actuators.

MXene, renowned for its natural "quantum-confined-superfluidic" (QSF) channels, demonstrates superior electrical/thermal conductivity, favorable hydrophilicity, and remarkable mechanical strength, rendering it an ideal candidate for multiresponsive actuators, which are promising for soft electronics and robots. Currently, most MXene-based actuators are mainly prepared by combining an active layer and an inner layer, with only a few utilizing regulated QSF channels. However, tailoring QSF channels for multiresponsive actuators is extremely challenging. Herein, we introduce a multiresponsive graphene oxide (GO)&Fe3O4/MXene actuator that can respond to humidity, light, heat, electricity, and magnetic fields by constructing asymmetric QSF channels. The asymmetric water adsorption, transportation, and desorption behaviors, controlled by the different QSF channels between the GO&Fe3O4 layer and the MXene layer, enable the multiresponsiveness of the actuator. As proof-of-concept demonstrations, several smart devices, such as a bionic crab-like crawler, a transporting flower robot, and a smart gripper, are prepared, holding great potential for advancing future soft robotics.

Tunicate cellulose nanocrystals strengthened injectable stretchable hydrogel as multi-responsive enhanced antibacterial wound dressing for promoting diabetic wound healing.

The intricate microenvironment of diabetic wounds characterized by hyperglycemia, intense oxidative stress, persistent bacterial infection and complex pH fluctuations hinders the healing process. Herein, an injectable multifunctional hydrogel (QPTx) was developed, which exhibited excellent mechanical performance and triple responsiveness to pH, temperature, and glucose due to dynamic covalent cross-linking involving dynamic Schiff base bonds and phenylboronate esters with phenylboronic-modified quaternized chitosan (QCS-PBA), polydopamine coated tunicate cellulose crystals (PDAn@TCNCs) and polyvinyl alcohol (PVA). Furthermore, the hydrogels can incorporate insulin (INS) drugs to adapt to the complex and variable wound environment in diabetic patients for on-demand drug release that promote diabetic wound healing. Based on various excellent properties of the colloidal materials, the hydrogels were evaluated for self-healing, rheological and mechanical properties, in vitro insulin response to pH/temperature/glucose release, antibacterial, antioxidant, tissue adhesion, coagulation, hemostasis in vivo and in vitro, and biocompatibility and biodegradability. By introducing PDAn@TCNCs particles, the hydrogel has photothermal antibacterial activity, enhanced adhesion and oxidation resistance. We further demonstrated that these hydrogel dressings significantly improved the healing process compared to commercial dressings (Tegaderm™) in full-layer skin defect models. All indicated that the glucose-responsive QPTx hydrogel platform has great potential for treating diabetic wounds.

Multiresponsive Bilayer Hydrogel Actuator with Switchable Shape Morphing Capability and Visible Color/Fluorescence Change.

Bilayer hydrogels, endowed with multiresponsive and switchable color-changing properties, have garnered significant attention for bioinspired artificial intelligent materials. However, the design and fabrication of such hydrogels that can fully mimic the adaptation of the live organism, i.e., simultaneous changes in shape, fluorescent, and/or visible color, still remain significant challenges. Herein, a multiresponsive (e.g., temperature, salt, and pH) and multiadaptive (shape, fluorescent color, and visible color changes) hydrogel was fabricated by employing monomers featuring pH-responsive fluorescence 4-(2-(4-(dimethylamino) phenyl)-1-isocyanovinyl) phenol (DP) and switchable color-changing 4-(2-sulfethyl) -1-(4-vinylbenzyl) pyridinium betaine (VPES). The bilayer hydrogel comprises a temperature- and pH-responsive gel layer, poly(N-isopropylacrylamide-co-2-(dimethylamino) ethyl methacrylate), along with a pH-, temperature-, and salt-responsive gel layer, poly(acrylamide-co-2-(dimethylamino)ethyl methacrylate-co-VPES)@DP. Due to the opposite swelling/shrinking behavior between the two layers, the prepared hydrogel exhibits shape changes in response to thermal, salt, and pH stimuli, along with switchable fluorescent color and visible color change that originate from DP and polyVPES, respectively. Apart from multiresponsive behavior, this hydrogel also shows an excellent antifatigue property and high sensitivity, which makes it hold significant potential in many applications. We anticipate that this strategy to realize multiresponsive capability in this work can also inspire the design of the biomimetic smart materials.

Polymersomes as Innovative, Stimuli-Responsive Platforms for Cancer Therapy.

This review addresses the urgent need for more targeted and less toxic cancer treatments by exploring the potential of multi-responsive polymersomes. These advanced nanocarriers are engineered to deliver drugs precisely to tumor sites by responding to specific stimuli such as pH, temperature, light, hypoxia, and redox conditions, thereby minimizing the side effects associated with traditional chemotherapy. We discuss the design, synthesis, and recent applications of polymersomes, emphasizing their ability to improve therapeutic outcomes through controlled drug release and targeted delivery. Moreover, we highlight the critical areas for future research, including the optimization of polymersome-biological interactions and biocompatibility, to facilitate their clinical adoption. Multi-responsive polymersomes emerge as a promising development in nanomedicine, offering a pathway to safer and more effective cancer treatments.