Optically Mediated Hydrogel-Based Ionic Diode.

Ionic diodes with environmentally modulated ion-rectifying characteristics have attracted much attention and show great promise in the construction of smart devices with environmental adaptability. One immediate challenge is to integrate stimuli responsiveness and ion rectification into one single ionic diode, which requires a close cooperation of chemical principles and device technologies. Herein, an ionic diode based on a photoresponsive hydrogel with optically mediated ion-rectifying performances is introduced. Relying on the photoresponsive concentration of proton in the hydrogel, the ionic current rectification can be prominently enhanced upon ultraviolet (UV) irradiation. A maximum ionic current rectification ratio of the optically mediated ionic diode about 4 × 105 is achieved. Furthermore, the hydrogel-based diode can serve as an AND logic gate operated by UV light and voltage bias as two independent inputs. As a proof of concept, to use the optically mediated diode is achieved to modulate the feedback of a robot with logic behaviors. This work provides a novel and valuable strategy for designing functional hydrogel-based devices with the integration of stimuli-responsiveness and logic signal processing through chemical approaches.

Solid-State Cholesteric Liquid Crystals as an Emerging Platform for the Development of Optical Photonic Sensors.

Over the past decade, solid-state cholesteric liquid crystals (CLCsolid ) have emerged as a promising photonic material, heralding new opportunities for the advancement of optical photonic biosensors and actuators. The periodic helical structure of CLCsolid s gives rise to their distinctive capability of selectively reflecting incident radiation, rendering them highly promising contenders for a wide spectrum of photonic applications. Extensive research is conducted on utilizing CLCsolid 's optical characteristics to create optical sensors for bioassays, diagnostics, and environmental monitoring. This review provides an overview of emerging technologies in the field of interpenetrating polymeric network-CLCsolid (IPN) and CLCsolid -based optical sensors, including their structural designs, processing, essential materials, working principles, and fabrication methodologies. The review concludes with a forward-looking perspective, addressing current challenges and potential trajectories for future research.

Light and Heat-Driven Flexible Solid Supramolecular Polymer Displaying Phosphorescence and Reversible Photochromism.

Herein, a type of light- and heat-driven flexible supramolecular polymer with reversibly long-lived phosphorescence and photochromism is constructed from acrylamide copolymers with 4-phenylpyridinium derivatives containing a cyano group (P-CN, P-oM, P-mM), sulfobutylether-ß-cyclodextrin (SBCD), and polyvinyl alcohol (PVA). Compared to their parent solid polymers, these flexible supramolecules based on the non-covalent cross-linking of copolymers, SBCD, and PVA efficiently boost the phosphorescence lifetimes (723.0 ms for P-CN, 623.0 ms for P-oM, 945.8 ms for P-mM) through electrostatic interaction and hydrogen bonds. The phosphorescence intensity/lifetime, showing excellent responsiveness to light and heat, sharply decreased after irradiation with a 275 nm flashlight or sunlight and gradually recovered through heating. This is accompanied by the occurrence and fading of visible photochromism, manifesting as dark green for P-CN and pink for P-oM and P-mM. These reversible photochromism and phosphorescence behaviors are mainly attributed to the generation and disappearance of organic radicals in the 4-phenylpyridinium derivatives with a cyano group, which can guide tunable luminescence and photochromism.

Custom-Design of Multi-Stimuli-Responsive Degradable Silica Nanoparticles for Advanced Cancer-Specific Chemotherapy.

Chemotherapy is crucial in oncology for combating malignant tumors but often encounters obatacles such as severe adverse effects, drug resistance, and biocompatibility issues. The advantages of degradable silica nanoparticles in tumor diagnosis and treatment lie in their ability to target drug delivery, minimizing toxicity to normal tissues while enhancing therapeutic efficacy. Moreover, their responsiveness to both endogenous and exogenous stimuli opens up new possibilities for integrating multiple treatment modalities. This review scrutinizes the burgeoning utility of degradable silica nanoparticles in combination with chemotherapy and other treatment modalities. Commencing the elucidation of degradable silica synthesis and degradation mechanisms, emphasis is placed on the responsiveness of these materials to endogenous (e.g., pH, redox reactions, hypoxia, and enzymes) and exogenous stimuli (e.g., light and high-intensity focused ultrasound). Moreover, this exploration delves into strategies harnessing degradable silica nanoparticles in chemotherapy alone, coupled with radiotherapy, photothermal therapy, photodynamic therapy, gas therapy, immunotherapy, starvation therapy, and chemodynamic therapy, elucidating multimodal synergies. Concluding with an assessment of advances, challenges, and constraints in oncology, despite hurdles, future investigations are anticipated to augment the role of degradable silica in cancer therapy. These insights can serve as a compass for devising more efficacious combined tumor treatment strategies.

Application of Organic Gel on Skin Realized by Hydrogel/Organic Gel Adhesion.

Diversity in solvent selection bestows the organic gel with appealing characteristics embracing antidrying, anti-icing, and antifouling abilities. However, organic gel, subjected to the "toxic" inherent property of solvent, is not able to be manipulated on skin. Herein, introducing the hydrogel layer amid organic gel and skin is envisaged to realize application of organic gel on skin. Hydrogel, inserted as the medium layer, works for the coupling role between skin and organic gel, also avoids the direct contact of organic gel toward skin. First, hydrogel system composed of acrylic acid is fabricated, meanwhile organic gel is prepared employing 2-hydroxyethyl methacrylate, ethylene glycol (EG) as solvent. Organic gel is able to adhere to hydrogel by hydrogen bonding resulting from carboxyl groups of polyacrylic acid chains and hydroxyl groups occurring on 2-hydroxyethyl methacrylate or EG. Additionally, hydrogen bonding enables the hydrogel to be firmly attached to skin, thus organic gel/hydrogel/skin assembly is produced. The further application of organic gel is exploited by incorporating stimuli-responsive dyes including spiropyran and rhodamine derivative.

Responsive Supramolecular Polymers for Diagnosis and Treatment.

Stimuli-responsive supramolecular polymers are ordered nanosized materials that are held together by non-covalent interactions (hydrogen-bonding, metal-ligand coordination, π-stacking and, host-guest interactions) and can reversibly undergo self-assembly. Their non-covalent nature endows supramolecular polymers with the ability to respond to external stimuli (temperature, light, ultrasound, electric/magnetic field) or environmental changes (temperature, pH, redox potential, enzyme activity), making them attractive candidates for a variety of biomedical applications. To date, supramolecular research has largely evolved in the development of smart water-soluble self-assemblies with the aim of mimicking the biological function of natural supramolecular systems. Indeed, there is a wide variety of synthetic biomaterials formulated with responsiveness to control and trigger, or not to trigger, aqueous self-assembly. The design of responsive supramolecular polymers ranges from the use of hydrophobic cores (i.e., benzene-1,3,5-tricarboxamide) to the introduction of macrocyclic hosts (i.e., cyclodextrins). In this review, we summarize the most relevant advances achieved in the design of stimuli-responsive supramolecular systems used to control transport and release of both diagnosis agents and therapeutic drugs in order to prevent, diagnose, and treat human diseases.

Oligo-Adenine Derived Secondary Nucleic Acid Frameworks: From Structural Characteristics to Applications.

Oligo-adenine (polyA) is primarily known for its critical role in mRNA stability, translational status, and gene regulation. Beyond its biological functions, extensive research has unveiled the diverse applications of polyA. In response to environmental stimuli, single polyA strands undergo distinctive structural transitions into diverse secondary configurations, which are reversible upon the introduction of appropriate counter-triggers. In this review, we systematically summarize recent advances of noncanonical structures derived from polyA, including A-motif duplex, A-cyanuric acid triplex, A-coralyne-A duplex, and T·A-T triplex. The structural characteristics and mechanisms underlying these conformations under specific external stimuli are addressed, followed by examples of their applications in stimuli-responsive DNA hydrogels, supramolecular fibre assembly, molecular electronics and switches, biosensing and bioengineering, payloads encapsulation and release, and others. A detailed comparison of these polyA-derived noncanonical structures is provided, highlighting their distinctive features. Furthermore, by integrating their stimuli-responsiveness and conformational characteristics, advanced material development, such as pH-cascaded DNA hydrogels and supramolecular fibres exhibiting dynamic structural transitions adapting environmental cues, are introduced. An outlook for future developments is also discussed. These polyA derived, stimuli-responsive, noncanonical structures enrich the arsenal of DNA "toolbox", offering dynamic DNA frameworks for diverse future applications.

Reversible Local Protonation-Deprotonation: Tuning Stimuli-Responsive Circularly Polarized Luminescence in Chiral Hybrid Zinc Halides for Anti-Counterfeiting and Encryption.

Precise control over the organic composition is crucial for tailoring the distinctive structures and properties of hybrid metal halides. However, this approach is seldom utilized to develop materials that exhibit stimuli-responsive circularly polarized luminescence (CPL). Herein, we present the synthesis and characterization of enantiomeric hybrid zinc bromides: biprotonated ((R/S)-C12H16N2)ZnBr4 ((R/S-LH2)ZnBr4) and monoprotonated ((R/S)-C12H15N2)2ZnBr4 ((R/S-LH1)2ZnBr4), derived from the chiral organic amine (R/S)-2,3,4,9-Tetrahydro-1H-carbazol-3-amine ((R/S)-C12H14N2). These compounds showcase luminescent properties; the zero-dimensional biprotonated form emits green light at 505 nm, while the monoprotonated form, with a pseudo-layered structure, displays red luminescence at 599 and 649 nm. Remarkably, the reversible local protonation-deprotonation behavior of the organic cations allows for exposure to polar solvents and heating to induce reversible structural and luminescent transformations between the two forms. Theoretical calculations reveal that the lower energy barrier associated with the deprotonation process within the pyrrole ring is responsible for the local protonation-deprotonation behavior observed. These enantiomorphic hybrid zinc bromides also exhibit switchable circular dichroism (CD) and CPL properties. Furthermore, their chloride counterparts were successfully obtained by adjusting the halogen ions. Importantly, the unique stimuli-responsive CPL characteristics position these hybrid zinc halides as promising candidates for applications information storage, anti-counterfeiting, and information encryption.

Inducing and Switching the Handedness of Polyacetylenes with Topologically Chiral [2]Catenane Pendants.

To explore the chirality induction and switching of topological chirality, poly[2]catenanes composed of helical poly(phenylacetylenes) (PPAs) main chain and topologically chiral [2]catenane pendants are described for the first time. These poly[2]catenanes with optically active [2]catenanes on side chains were synthesized by polymerization of enantiomerically pure topologically chiral [2]catenanes with ethynyl polymerization site and/or point chiral moiety. The chirality information of [2]catenane pendants was successfully transferred to the main chain of polyene backbones, leading to preferred-handed helical conformations, while the introduction of point chiral units has negligible effect on the overall helices. More interestingly, attributed to unique dynamic feature of the [2]catenane pendants, these polymers revealed dynamic response behaviors to solvents, temperature, and sodium ions, resulting in the fully reversible switching on/off of the chirality induction. This work provides not only new design strategy for novel chiroptical switches with topologically chiral molecules but also novel platforms for the development of smart chiral materials.

Lighting Up Bispyrene-Functionalized Chiral Molecular Muscles with Switchable Circularly Polarized Excimer Emissions.

Aiming at the further extension of the application scope of traditional molecular muscles, a novel bispyrene-functionalized chiral molecular [c2]daisy chain was designed and synthesized. Taking advantage of the unique dimeric interlocked structure of molecular [c2]daisy chain, the resultant chiral molecular muscle emits strong circularly polarized luminescence (CPL) attributed to the pyrene excimer with a high dissymmetry factor (glum) value of 0.010. More importantly, along with the solvent- or anion- induced motions of the chiral molecular muscle, the precise regulation of the pyrene stacking within its skeleton results in the switching towards either "inversed" state with sign inversion and larger glum values or "down" state with maintained handedness and smaller glum values, making it a novel multistate CPL switch. As the first example of chiral molecular muscle-based CPL switch, this proof-of-concept study not only successfully widens the application scopes of molecular muscles, but also provides a promising platform for the construction of novel smart chiral luminescent materials for practical applications.

Stimuli-Responsive Multifunctional Nanomedicine for Enhanced Glioblastoma Chemotherapy Augments Multistage Blood-to-Brain Trafficking and Tumor Targeting.

Minimal therapeutic advances have been achieved over the past two decades for glioblastoma (GBM), which remains an unmet clinical need. Here, hypothesis-driven stimuli-responsive nanoparticles (NPs) for docetaxel (DTX) delivery to GBM are reported, with multifunctional features that circumvent insufficient blood-brain barrier (BBB) trafficking and lack of GBM targeting-two major hurdles for anti-GBM therapies. NPs are dual-surface tailored with a i) brain-targeted acid-responsive Angiopep-2 moiety that triggers NP structural rearrangement within BBB endosomal vesicles, and ii) L-Histidine moiety that provides NP preferential accumulation into GBM cells post-BBB crossing. In tumor invasive margin patient cells, the stimuli-responsive multifunctional NPs target GBM cells, enhance cell uptake by 12-fold, and induce three times higher cytotoxicity in 2D and 3D cell models. Moreover, the in vitro BBB permeability is increased by threefold. A biodistribution in vivo trial confirms a threefold enhancement of NP accumulation into the brain. Last, the in vivo antitumor efficacy is validated in GBM orthotopic models following intratumoral and intravenous administration. Median survival and number of long-term survivors are increased by 50%. Altogether, a preclinical proof of concept supports these stimuli-responsive multifunctional NPs as an effective anti-GBM multistage chemotherapeutic strategy, with ability to respond to multiple fronts of the GBM microenvironment.

Muscle-Like Supramolecular Polymers with Dual Motion Patterns.

Benefiting from the features like polymeric linear structures, stimuli-responsiveness and dynamic adaptiveness, supramolecular polymers (SPs) are favored as exploiting muscle-like materials, allowing for imitating the muscle functions. However, a substantial part of these materials barely owned an unitary motion orientation while it was obviously known that muscle movements involved distinct orientations. Herein, M1 holding the structure of 44-membered macrocycle with two aldehyde groups was designed, meanwhile, M2 comprising of secondary ammonium ions, 3,5-di-tert-butylphenyl groups as well as the alkyl chains was fabricated, for which it could be assembled with M1 to generate SPs based on host-guest interactions from a large macrocycle and two secondary ammonium ions. SPs underwent vertical compression upon the addition of N2 H4 owing to the forming dynamic covalent bonds, notably, mechanically interlocked structures were also generated. Afterwards, the vertically compressed SPs experienced horizontal shrinkage when tetrabutylammonium chloride was contributed due to the destruction of host-guest interactions.

Self-Healable, Regenerable, and Degradable Dynamic Covalent Nitroalcohol Organogels.

Dynamic covalent gels are synthesized from an aromatic trialdehyde and α,ω-dinitroalkanes via the nitroaldol reaction in organic solvents. The gelation process can be fine-tuned by changing the starting nitroalkanes, solvents, feed concentration, catalyst loading, or reaction temperature. The resulting organogels demonstrate good structural integrity and excellent self-healing ability. Intact xerogels are produced upon drying, without damaging the network, and the solvent-free network can recover its gel form in the presence of an organic solvent. Furthermore, the crosslinked dynameric gel depolymerize to small molecules in response to excess nitromethane.

Molecularly Imprinted Nanomaterials with Stimuli Responsiveness for Applications in Biomedicine.

The review aims to summarize recent reports of stimuli-responsive nanomaterials based on molecularly imprinted polymers (MIPs) and discuss their applications in biomedicine. In the past few decades, MIPs have been proven to show widespread applications as new molecular recognition materials. The development of stimuli-responsive nanomaterials has successfully endowed MIPs with not only affinity properties comparable to those of natural antibodies but also the ability to respond to external stimuli (stimuli-responsive MIPs). In this review, we will discuss the synthesis of MIPs, the classification of stimuli-responsive MIP nanomaterials (MIP-NMs), their dynamic mechanisms, and their applications in biomedicine, including bioanalysis and diagnosis, biological imaging, drug delivery, disease intervention, and others. This review mainly focuses on studies of smart MIP-NMs with biomedical perspectives after 2015. We believe that this review will be helpful for the further exploration of stimuli-responsive MIP-NMs and contribute to expanding their practical applications especially in biomedicine in the near future.

Dimension Engineering of Stimuli-Responsive 1D Molecular Crystals into Unusual 2D and 3D Zigzag Waveguides.

We demonstrate an innovative technique to achieve organic 2D and 3D waveguides with peculiar shapes from an acicular, stimuli-responsive molecular crystal, (2Z,2'Z)-3,3'-(anthracene-9,10-diyl)bis(2-(3,5-bis(trifluoromethyl)phenylacrylonitrile), Ant-CF3 . The greenish-yellow fluorescent (FL) Ant-CF3 molecular crystals exhibit laser power-dependent permanent mechanical bending in 2D and 3D. Investigation of a single-crystal using spatially-resolved Raman/FL/electron microscopy, and theoretical calculations revealed photothermal (Z,E)/(E,E) isomerization-assisted transition from crystalline to amorphous phase at the laser-exposed regions. This phenomenon facilitates the dimension engineering of a 1D crystal waveguide into 2D waveguide on a substrate or a 3D waveguide in free space. The bends can be used as interconnection points to couple different optical elements. The presented technique has broader implications in organic photonics and other crystal-related photonic technologies.

pH- and Redox-Responsive Pickering Emulsions Based on Cellulose Nanocrystal Surfactants.

Nanoparticle surfactants (NPSs), formed by using dynamic interactions between nanoparticles and complementary ligands at the liquid-liquid interface, have emerged as "smart emulsifiers" with attributes of high emulsification efficiency, long-term stability, and on-demand emulsification/demulsification capabilities. However, only pH-responsiveness can be adopted for the assembly of reported NPSs formed by electrostatic interactions. Here, we propose an alternative design strategy, by taking advantage of the ferrocenium (Fc+ ) sulfate ion pair, to develop a new type of cellulose nanocrystal (CNC) surfactant. The Fc+ groups are sensitive to pH, redox reagents and voltage, imparting the CNC surfactants and derived Pickering emulsions with multi-stimuli-responsiveness, and showing promising applications in controllable delivery, release, and biphasic biocatalysis.

Installing Reduction Responsiveness into Biomolecules by Introducing Nitroaryl Groups.

Artificially synthesized stimuli-responsive biomolecules are attractive as molecular tools for monitoring and modulating biological systems. In biological systems, redox stimuli are common, and their dysregulation is typically linked to various abnormal or disease states. In this Concept article, the molecular design of reduction-responsive biomolecules, such as peptides, nucleic acids, and saccharides, which are produced by introducing nitroaryl groups into them, is reviewed with a special emphasis on simple 4-nitrobenzene-based motifs.

Recent Advances in Peptides-Based Stimuli-Responsive Materials for Biomedical and Therapeutic Applications: A Review.

Smart materials are engineered materials that have one or more properties that are introduced in a controlled fashion by surrounding stimuli. Engineering of biomacromolecules like proteins into a smart material call for meticulous artistry. Peptides have grabbed notable attention as a preferred source for smart materials in the medicinal field, promoted by their versatile chemical and biophysical attributes of biocompatibility, and biodegradability. Recent advances in the synthesis of multifunctional peptides have proliferated their application in diverse domains: agriculture, nanotechnology, medicines, biosensors, therapeutics, and soft robotics. Stimuli such as pH, temperature, light, metal ions, and enzymes have vitalized physicochemical properties of peptides by augmented sensitivity, stability, and selectivity. This review elucidates recent (2018-2021) advances in the design and synthesis of smart materials, from stimuli-responsive peptides followed by their biomedical and therapeutic applications.

Dual-Responsive Glycopolymers for Intracellular Codelivery of Antigen and Lipophilic Adjuvants.

Traditional approaches to vaccines use whole organisms to trigger an immune response, but they do not typically generate robust cellular-mediated immunity and have various safety risks. Subunit vaccines composed of proteins and/or peptides represent an attractive and safe alternative to whole organism vaccines, but they are poorly immunogenic. Though there are biological reasons for the poor immunogenicity of proteins and peptides, one other key to their relative lack of immunogenicity could be attributed to the poor pharmacokinetic properties of exogenously delivered proteins and peptides. For instance, peptides often aggregate at the site of injection and are not stable in biological fluids, proteins and peptides are rapidly cleared from circulation, and both have poor cellular internalization and endosomal escape. Herein, we developed a delivery system to address the lack of protein immunogenicity by overcoming delivery barriers as well as codelivering immune-stimulating adjuvants. The glycopolymeric nanoparticles (glycoNPs) are composed of a dual-stimuli-responsive block glycopolymer, poly[2-(diisopropylamino)ethyl methacrylate]-b-poly[(pyridyl disulfide ethyl methacrylate)-co-(methacrylamidoglucopyranose)] (p[DPA-b-(PDSMA-co-MAG)]). This polymer facilitates protein conjugation and cytosolic release, the pH-responsive release of lipophilic adjuvants, and pH-dependent membrane disruption to ensure cytosolic delivery of antigens. We synthesized p[DPA-b-(PDSMA-co-MAG)] by reversible addition-fragmentation chain transfer (RAFT) polymerization, followed by the formation and physicochemical characterization of glycoNPs using the p[DPA-b-(PDSMA-co-MAG)] building blocks. These glycoNPs conjugated the model antigen ovalbumin (OVA) and released OVA in response to elevated glutathione levels. Moreover, the glycoNPs displayed pH-dependent drug release of the model hydrophobic drug Nile Red while also exhibiting pH-responsive endosomolytic behavior as indicated by a red blood cell hemolysis assay. GlycoNPs coloaded with OVA and the toll-like receptor 7/8 (TLR-7/8) agonist Resiquimod (R848) activated DC 2.4 dendritic cells (DCs) significantly more than free OVA and R848 and led to robust antigen presentation of the OVA epitope SIINFEKL on major histocompatibility complex I (MHC-I). In sum, the dual-stimuli-responsive glycopolymer introduced here overcomes major protein and peptide delivery barriers and could vastly improve the immunogenicity of protein-based vaccines.

Stimuli-Responsive Transformable Supramolecular Nanotubes.

Supramolecular nanotubes produced by self-assembly of organic molecules can have unique structural features such as a one-dimensional morphology with no branching, distinguishable inner and outer surfaces and membrane walls, or a structure that is hollow and has a high aspect ratio. Incorporation of functional groups that respond to external chemical or physical stimuli into the constituent organic molecules of supramolecular nanotubes allows us to drastically change the structure of the nanotubes by applying such stimuli. This ability affords an array of controllable approaches for the encapsulation, storage, and release of guest compounds, which is expected to be useful in the fields of physics, chemistry, biology, and medicine. In this article, I review the supramolecular nanotubes developed by our group that exhibit morphological transformations in response to pH, chemical reaction, light, temperature, or moisture.