Multi‐Stimuli‐Responsive Polymeric Materials

Stimuli‐responsive materials are of immense importance because of their ability to undergo alteration of their properties in response to their environment. The properties of such materials can be tuned by subtle adjustments in temperature, pH, light, and so forth. Among such smart materials, multi‐stimuli‐responsive polymeric materials are of pronounced significance as they offer a wide range of applications and their properties can be tuned through several mechanisms. Here, we aim to highlight some recent studies showcasing the multi‐stimuli‐responsive character of these polymers, which are still relatively little known compared to their single‐stimuli‐responsive counterpart.     

Self‐Storage: A Novel Family of Stimuli‐Responsive Polymer Materials for Optical and Electrochemical Switching

For most stimuli‐responsive polymer materials (SRPMs), such as polymer gels, micelles, and brushes, the responsive mechanism is based on the solubility or compatibility with liquid media. That basis always results in distorting or collapsing the material's appearance and relies on external liquids. Here, a novel kind of SRPMs is proposed. Unlike most SRPMs, liquid is stored within special domains rather than expelled, so it is deforming‐free and relying on no external liquid, which is referred to as self‐storage SRPMs (SS‐SRPMs). The facile and universal route to fabricate SS‐SRPMs allows for another novel family of SRPMs. Furthermore, it is validated that SS‐SRPMs can drastically respond to outside temperature like switchers, especially for optical and electrochemical responses. Those features hold prospects for applications in functional devices, such as smart optical lenses or anti‐self‐discharge electrolytes for energy devices.

     

Smart Nanocontainers: Progress on Novel Stimuli‐Responsive Polymer Vesicles

In the past decade, polymer vesicles prepared by self‐assembly techniques have attracted increasing scientific interest based on their unique features highlighted with tunable membrane properties, versatility, stability, and capacity of transporting hydrophilic as well as hydrophobic species. Polymersomes exhibit intriguing potential applications such as cell mimicking dimensions and functions, tunable delivery vehicles, for the templating of biomineralization, nanoreactors, and as scaffolds for biological conjugation. In this Feature Article, an overview of the preparation and application of recently developed “smart” polymer vesicles, which can respond to the novel external stimuli, including carbon dioxide (CO₂), electrochemical potential, ultrasound, enzyme, near‐infrared light, and magnetic field is given. The response mechanism and morphology change are explored with specific focus on the functionalization of various domains of the polymer vesicles. In addition, the current limitations are explored as well as the challenges facing the development of these nanostructures toward real‐world applications.

     

Tunable Metal‐Enhanced Fluorescence by Stimuli‐Responsive Polyelectrolyte Interlayer Films

In this paper, we report on the tunable metal‐enhanced fluorescence (MEF) of Ag nanostructures. Because of the good MEF properties of the highly dendritic Ag nanostructures, we obtained an increase of up to 25 times for the weak fluorescence of porphyrin molecules (Por^4–). More importantly, by the introduction of a stimulus‐responsive PAA/PDDA multilayer film as an interlayer, the distance between the fluorophores and the Ag nanostructures could be tuned by immersing the substrates into solutions of different ionic strength or pH. The MEF behavior of the composite films could thus be tuned in a controlled manner, because of the distance dependent nature of the MEF effects.

     

Double Metal Ions Competitively Control the Guest‐Sensing Process: A Facile Approach to Stimuli‐Responsive Supramolecular Gels

A facile approach to the design of stimuli‐responsive supramolecular gels (SRSGs) termed double‐metal‐ion competitive coordination control is reported. By this means, the fluorescence signals and guest‐selective responsiveness of the SRSGs are controlled by the competitive coordination of two different metal ions with the gelators and the target guest. To demonstrate this approach, a gelator G2 based on multiple self‐assembly driving forces was synthesized. G2 could form Ca²⁺‐coordinated metallogel CaG with strong aggregation‐induced emission (AIE). Doping of CaG with Cu²⁺ results in AIE quenching of CaG and formation of Ca²⁺‐ and Cu²⁺‐based metallogel CaCuG. CaCuG could fluorescently detect CN^? with specific selectivity through the competitive coordination of CN^? with the Cu²⁺ and the coordination of Ca²⁺ with G2 again. This approach may open up routes to novel stimuli‐responsive supramolecular materials.     

Multifunctional Hydrogels with Temperature,Ion, and Magnetocaloric Stimuli‐Responsive Performances

In this work, multifunctional hydrogels with vivid color change and shrinking–swelling response to temperature, ion strength, and alternating magnetic field are fabricated via magnetic assembly. The hydrogels show gradual shift colors from yellowish green to green, cyan, blue, purple, and even reddish violet in response to temperature or ion strength. In the response process, the whole color modulation process is fully reversible and transferable along with a relative short response time. Especially, the magnetism and porous structure of the hybrid hydrogel enable it to be a potential carrier for hydrophobic molecules. Taking advantage of the magnetocaloric responsiveness, the dyed oil loaded hydrogel exhibits a controllable release behavior in each reversible shrinking–swelling cycle under an alternating magnetic field. This multi‐responsive hydrogel can hold promise for practical engineering applications, including sensors, displays, and controlled release.

     

Stimuli‐Responsive Water‐Soluble Fullerene (C60) Polymeric Systems

This review documents the advances in stimuli‐responsive water‐soluble fullerene (C₆₀) polymeric systems. Stimuli‐responsive polymers, when grafted onto C₆₀ impart “smart” and “responsive” characteristics, and these novel materials adopt various morphologies when subjected to external stimuli, such as pH, temperature, and salt. Various synthetic approaches for producing C₆₀‐polymers are outlined and discussed. The responsive behavior, water solubility, and self‐assembly characteristics of these C₆₀‐polymers make them attractive for applications such as drug delivery, temperature sensors, and personal care.     

Rapid,On‐Command Debonding of Stimuli‐Responsive Cross‐Linked Adhesives by Continuous,Sequential Quinone Methide Elimination Reactions

Adhesives that selectively debond from a surface by stimuli‐induced head‐to‐tail continuous depolymerization of poly(benzyl ether) macro‐cross‐linkers within a poly(norbornene) matrix are described. Continuous head‐to‐tail depolymerization provides faster rates of response than can be achieved using a small‐molecule cross‐linker, as well as responses to lower stimulus concentrations. Shear‐stress values for glass held together by the adhesive reach 0.51±0.10 MPa, whereas signal‐induced depolymerization via quinone methide intermediates reduces the shear stress values to 0.05±0.02 MPa. Changing the length of the macro‐cross‐linkers alters the time required for debonding, and thus enables the programmed sequential release of specific layers in a glass composite material.     

Multi‐Stimuli‐Responsive Polymeric Prodrug for Enhanced Cancer Treatment

Accomplishing efficient delivery of a nanomedicine to the tumor site will encounter two contradictions as follows: 1) a contradiction between prolonged circulation time and endocytosis by cancer cells; 2) a dilemma between the stability of nanomedicine during blood circulation and intracellular drug release. While developing a nanomedicine which can solve the above two contradictions simultaneously is still a challenge, here, a multi‐stimuli‐responsive polymeric prodrug (PLys‐co‐(PLys‐DA)‐co‐(PLys‐SS‐PTX))‐b‐PLGLAG‐mPEG (P‐PEP‐SS‐PTX‐DA) is synthesized which is multi‐sensitive to overexpressed matrix metalloproteinase‐2 (MMP‐2), low pH, and high concentration of glutathione in tumors. The P‐PEP‐SS‐PTX‐DA can be dePEGylated and reversed from negative at normal physiological pH to positive charge at tumor extracellular microenvironment; in this way, it can solve the contradiction between prolonged circulation time and endocytosis by cancer cells. Owing to the high reductive conditions in cancer cells, P‐PEP‐SS‐PTX‐DA is ruptured to release paclitaxel (PTX) intracellular efficiently; therefore, it can resolve the dilemma between the stability of nanomedicine during blood circulation and intracellular drug release. These indicate that the multi‐stimuli‐responsive polymeric prodrug has potential application prospects in drug delivery and cancer therapy.     

Multi‐Stimuli‐Responsive Organometallic Gels Based on Ferrocene‐Linked Poly(Aryl Ether) Dendrons: Reversible Redox Switching and Pb2+‐Ion Sensing

We describe the design, synthesis, and “stimuli‐responsive” study of ferrocene‐linked Fréchet‐type [poly(aryl ether)]‐dendron‐based organometallic gels, in which the ferrocene moiety is attached to the dendron framework through an acyl hydrazone linkage. The low‐molecular‐weight gelators (LMWGs) form robust gels in both polar and non‐polar solvent/solvent mixtures. The organometallic gels undergo stimuli‐responsive behavior through 1) thermal, 2) chemical, and 3) electrochemical methods. Among them, conditions 1 and 3 lead to seamlessly reversible with repeated cycles of identical efficiency. Results indicate that the flexible nature of the poly(aryl ether) dendron framework plays a key role in retaining the reversible electrochemical behavior of ferrocene moiety in the LMWGs. Further, the organometallic gelators have exhibited unique selectivity towards Pb²⁺ ions (detection limit ≈10^?8 M ). The metal ion‐sensing results in a gel–sol phase transition associated with a color change visible to the naked eye. Most importantly, decomplexing the metal ion from the system leads to the regeneration of the initial gel morphology, indicating the restoring ability of the organometallic gel. The metal–ligand binding nature has been analyzed by using ¹H NMR spectroscopy, mass spectrometry, and DFT calculations.     

Responsive Materials for Self‐Regulated Insulin Delivery

With diabetes mellitus becoming an important public health concern, insulin‐delivery systems are attracting increasing interest from both scientific and technological researchers. This feature article covers the present state‐of‐the‐art glucose‐responsive insulin‐delivery system (denoted as GRIDS), based on responsive polymer materials, a promising system for self‐regulated insulin delivery. Three types of GRIDS are discussed, based on different fundamental mechanisms of glucose‐recognition, with: a) glucose enzyme, b) glucose binding protein, and c) synthetic boronic acid as the glucose‐sensitive component. At the end, a personal perspective on the major issues yet to be worked out in future research is provided.     

An “Ingredients” Approach to Functional Self‐Synthesizing Materials: A Metal‐Ion‐Selective,Multi‐Responsive,Self‐Assembled Hydrogel

New methodology for making novel materials is highly desirable. Here, an “ingredients” approach to functional self‐assembled hydrogels was developed. By designing a building block to contain the right ingredients, a multi‐responsive, self‐assembled hydrogel was obtained through a process of template‐induced self‐synthesis in a dynamic combinatorial library. The system can be switched between gel and solution by light, redox reactions, pH, temperature, mechanical energy and sequestration or addition of Mg^II salt.     

Multi‐stimuli‐responsive self‐immolative polymer assemblies

Self‐immolative polymers (SIPs) undergo depolymerization in response to the cleavage of stimuli‐responsive end‐caps from their termini. Some classes of SIPs, including polycarbamates, have depolymerization rates that depend on environmental factors such as solvent and pH. In previous work, hydrophobic SIPs have been incorporated into amphiphilic block copolymers and used to prepare nanoassemblies. However, stimuli‐responsive hydrophilic blocks have not previously been incorporated. In this work, we synthesized amphiphilic copolymers composed of a hydrophobic polycarbamate SIP block and a hydrophilic poly(2‐(dimethylamino)ethyl methacrylate) (PDMAEMA) block connected by a UV light‐responsive linker end‐cap. It was hypothesized that after assembly of the block copolymers into nanoparticles, chain collapse of the PDMAEMA above its lower critical solution temperature (LCST) might change the environment of the SIP block, thereby altering its depolymerization rate. Self‐assembly of the block copolymers was performed, and the depolymerization of the resulting assemblies was studied by fluorescence spectroscopy, dynamic light scattering, and NMR spectroscopy. At 20 °C, the system exhibited a selective response to the UV light. At 65 °C, above the LCST of PDMAEMA, the systems underwent more rapid depolymerization, suggesting that the increase in rate arising from the higher temperature dominated over environmental effects arising from chain collapse. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 1868–1877     

Degradable Cationic Nanohydrogel Particles for Stimuli‐Responsive Release of siRNA

Well‐defined nanogels have become quite attractive as safe and stable carriers for siRNA delivery. However, to avoid nanoparticle accumulation, they need to provide a stimuli‐responsive degradation mechanism that can be activated at the payload's site of action. In this work, the synthetic concept for generating well‐defined nanohydrogel particles is extended to incorporate disulfide cross‐linkers into a cationic nanonetwork for redox‐triggered release of oligonucleotide payload as well as nanoparticle degradation under reductive conditions of the cytoplasm. Therefore, a novel disulfide‐modified spermine cross‐linker is designed that both allows disassembly of the nanogel as well as removal of cationic charge from residual polymer fragments. The degradation process is monitored by scanning electron microscopy (SEM) and fluorescence correlation spectroscopy (FCS). Moreover, siRNA release is analyzed by agarose gel electrophoresis and a fluorescent RNA detection assay. The results exemplify the versatility of the applied nanogel manufacturing process, which allows alternative stimuli‐responsive core cross‐linkers to be integrated for triggered oligonucleotide release as well as effective biodegradation for reduced nanotoxicity.