Multi‐Stimuli‐Responsive Microcapsules for Adjustable Controlled‐Release

Novel multi‐stimuli‐responsive microcapsules with adjustable controlled‐release characteristics are prepared by a microfluidic technique. The proposed microcapsules are composed of crosslinked chitosan acting as pH‐responsive capsule membrane, embedded magnetic nanoparticles to realize “site‐specific targeting”, and embedded temperature‐responsive sub‐microspheres serving as “micro‐valves”. By applying an external magnetic field, the prepared smart microcapsules can achieve targeting aggregation at specific sites. Due to acid‐induced swelling of the capsule membranes, the microcapsules exhibit higher release rate at specific acidic sites compared to that at normal sites with physiological pH. More importantly, through controlling the hydrodynamic size of sub‐microsphere “micro‐valves” by regulating the environment temperature, the release rate of drug molecules from the microcapsules can be flexibly adjusted. This kind of multi‐stimuli‐responsive microcapsules with site‐specific targeting and adjustable controlled‐release characteristics provides a new mode for designing “intelligent” controlled‐release systems and is expected to realize more rational drug administration.     

Poly(N‐isopropylacrylamide)‐Clay Nanocomposite Hydrogels with Responsive Bending Property as Temperature‐Controlled Manipulators

Novel poly(N‐isopropylacrylamide)‐clay (PNIPAM‐clay) nanocomposite (NC) hydrogels with both excellent responsive bending and elastic properties are developed as temperature‐controlled manipulators. The PNIPAM‐clay NC structure provides the hydrogel with excellent mechanical property, and the thermoresponsive bending property of the PNIPAM‐clay NC hydrogel is achieved by designing an asymmetrical distribution of nanoclays across the hydrogel thickness. The hydrogel is simply fabricated by a two‐step photo polymerization. The thermoresponsive bending property of the PNIPAM‐clay NC hydrogel is resulted from the unequal forces generated by the thermoinduced asynchronous shrinkage of hydrogel layers with different clay contents. The thermoresponsive bending direction and degree of the PNIPAM‐clay NC hydrogel can be adjusted by controlling the thickness ratio of the hydrogel layers with different clay contents. The prepared PNIPAM‐clay NC hydrogels exhibit rapid, reversible, and repeatable thermoresponsive bending/unbending characteristics upon heating and cooling. The proposed PNIPAM‐clay NC hydrogels with excellent responsive bending property are demonstrated as temperature‐controlled manipulators for various applications including encapsulation, capture, and transportation of targeted objects. They are highly attractive material candidates for stimuli‐responsive “smart” soft robots in myriad fields such as manipulators, grippers, and cantilever sensors.     

A pH‐Responsive Gating Membrane System with Pumping Effects for Improved Controlled Release

In this study, we report on a novel composite membrane system for pH‐responsive controlled release, which is composed of a porous membrane with linear grafted, positively pH‐responsive polymeric gates acting as functional valves, and a crosslinked, negatively pH‐responsive hydrogel inside the reservoir working as a functional pumping element. The proposed system features a large responsive release rate that goes effectively beyond the limit of concentration‐driven diffusion due to the pumping effects of the negatively pH‐responsive hydrogel inside the reservoir. The pH‐responsive gating membranes were prepared by grafting poly(methacrylic acid) (PMAA) linear chains onto porous polyvinylidene fluoride (PVDF) membrane substrates using a plasma‐graft pore‐filling polymerization, and the crosslinked poly(N,N‐dimethylaminoethyl methacrylate) (PDM) hydrogels were synthesized by free radical polymerization. The volume phase‐transition characteristics of PMAA and PDM were opposite. The proposed system opens new doors for pH‐responsive “smart” or “intelligent” controlled‐release systems, which are highly attractive for drug‐delivery systems, chemical carriers, sensors, and so on.     

A Drug‐Self‐Gated Mesoporous Antitumor Nanoplatform Based on pH‐Sensitive Dynamic Covalent Bond

To achieve on‐demand drug release, mesoporous silica nanocarriers as antitumor platforms generally need to be gated with stimuli‐responsive capping agents. Herein, a “smart” mesoporous nanocarrier that is gated by the drug itself through a pH‐sensitive dynamic benzoic–imine covalent bond is demonstrated. The new system, which tactfully bypasses the use of auxiliary capping agents, could also exhibit desirable drug release at tumor tissues/cells and enhanced tumor inhibition. Moreover, a facile dynamic PEGylation via benzoic–imine bond further endows the drug‐self‐gated nanocarrier with tumor extracellular pH‐triggered cell uptake and improves therapeutic efficiency in vivo. In short, the paradigm shift in capping agents here will simplify mesoporous nanomaterials as intelligent drug carriers for cancer therapy. Moreover, the self‐gated strategy in this work also shows general potential for self‐controlled delivery of natural biomolecules, for example, DNA/RNA, peptides, and proteins, due to their intrinsic amino groups.     

Kirigami‐Inspired Self‐Assembly of 3D Structures

Self‐assembly of 3D structures presents an attractive and scalable route to realize reconfigurable and functionally capable mesoscale devices without human intervention. A common approach for achieving this is to utilize stimuli‐responsive folding of hinged structures, which requires the integration of different materials and/or geometric arrangements along the hinges. It is demonstrated that the inclusion of Kirigami cuts in planar, hingeless bilayer thin sheets can be used to produce complex 3D shapes in an on‐demand manner. Nonlinear finite element models are developed to elucidate the mechanics of shape morphing in bilayer thin sheets and verify the predictions through swelling experiments of planar, millimeter‐scaled PDMS (polydimethylsiloxane) bilayers in organic solvents. Building upon the mechanistic understandings, The transformation of Kirigami‐cut simple bilayers into 3D shapes such as letters from the Roman alphabet (to make “ADVANCED FUNCTIONAL MATERIALS”) and open/closed polyhedral architectures is experimentally demonstrated. A possible application of the bilayers as tether‐less optical metamaterials with dynamically tunable light transmission and reflection behaviors is also shown. As the proposed mechanistic design principles could be applied to a variety of materials, this research broadly contributes toward the development of smart, tetherless, and reconfigurable multifunctional systems.     

Integrating Ionic Gate and Rectifier Within One Solid‐State Nanopore via Modification with Dual‐Responsive Copolymer Brushes

A dual‐functional nanofluidic device is demonstrated that integrates the ionic gate and the ionic rectifier within one solid‐state nanopore. The functionalities are realized by fabricating temperature‐ and pH‐responsive poly(N‐isopropyl acrylamide‐co‐acrylic acid) brushes onto the wall of a cone‐shaped nanopore. At ca. 25 °C, the nanopore works on a low ion conducting state. When the temperature is raised to ca. 40 °C, the nanopore switches to a high ion conducting state. The closing/opening of the nanopore results from the temperature‐triggered conformational transition of the attached copolymer brushes. Independently, in neutral and basic solutions, the conical nanopore rectifies the ionic current. While in acid solutions, no ion rectifying properties can be found. The charge properties of the copolymer brushes, combined with the asymmetrical pore geometry, render the nanopore a pH‐tunable ionic rectifier. The chemical modification strategy could be applied to incorporate other stimuli‐responsive materials for designing smart multi‐functional nanofluidic systems resembling the “live” creatures in nature.     

Microneedle‐Array Patch Fabricated with Enzyme‐Free Polymeric Components Capable of On‐Demand Insulin Delivery

Achieving persistent glycemic control in a painless and convenient way is the ultimate goal of diabetes management. Herein, an “enzyme‐free” polymeric microneedle (MN)‐array patch composed of a boronate‐containing hydrogel semi‐interpenetrated by biocompatible silk fibroin is developed. Consistent with the previous reports, the presence of the boronate‐hydrogel allows for glucose‐responsive diffusion‐control of insulin, while the crystalline fibroin component serves as a matrix‐stiffener to validate skin penetration. Remarkably, this “enzyme‐free” smart artificial on‐skin pancreas prototype remains stable for at least 2 months in an aqueous environment. Furthermore, it establishes sustained as well as acute glucose‐responsive insulin delivery, and is to the authors' knowledge, the first successful material design addressing such two technical challenges at once on an MN format. This long‐acting, on‐demand insulin delivery technology may offer a candidate for a next‐generation diabetes therapy that is remarkably stable, safe, economically efficient, and capable of providing both acute‐ and continuous glycemic control in a manner minimally dependent on patient compliance.     

Organic/Inorganic Hybrid Nanochannels Based on Polypyrrole‐Embedded Alumina Nanopore Arrays: pH‐ and Light‐Modulated Ion Transport

Inspired by the asymmetric structure and responsive ion transport in biological ion channels, organic/inorganic hybrid artificial nanochannels exhibiting pH‐modulated ion rectification and light‐regulated ion flux have been constructed by introducing conductive polymer into porous nanochannels. The hybrid nanochannels are achieved by partially modifying alumina (Al₂O₃) nanopore arrays with polypyrrole (PPy) layer using electrochemical polymerization, which results in an asymmetric component distribution. The protonation and deprotonation of Al₂O₃ and PPy upon pH variation break the surface charge continuity, which contributes to the pH‐tunable ion rectification. The ionic current rectification ratio is affected substantially by the pH value of electrolyte and the pore size of nanochannels. Furthermore, the holes (positive charges) in PPy layer induced by the cooperative effect of light and protons are used to regulate the ionic flux through the nanochannels, which results in a light‐responsive ion current. The magnitude of responsive ionic current could be amplified by optimizing this cooperation. This new type of stimuli‐responsive PPy/Al₂O₃ hybrid nanochannels features advantages of unique optical and electric properties from conducting PPy and high mechanical performance from porous Al₂O₃ membrane, which provide a platform for creating smart nanochannels system.     

Chain Extension of Stimuli‐Responsive Polymer Brushes: A General Strategy to Overcome the Drawbacks of the “Grafting‐To” Approach

Stimuli‐responsive polymer brushes are smart materials for the design of bio‐interactive and responsive interfaces. The “grafting‐to” approach is a convenient preparation procedure that allows the modification of surfaces with preformed and most notably well‐defined functionalized macromolecules. However, the shortcoming of this approach is an intrinsic limitation of the grafting density, which in turn affects the stimuli‐responsive properties of the brush system. Here, a general strategy to overcome this limitation and to simultaneously improve the switching behavior of a temperature‐responsive poly(N‐isopropylacrylamide) (PNiPAAm) brush is reported. A technically simple processing step is used in combination with the thermal azide–alkyne cycloaddition to perform the chain extension of alkyne‐functionalized PNiPAAm brushes with azide‐functionalized PNiPAAm molecules.     

pH‐Responsive Cyanine‐Grafted Graphene Oxide for Fluorescence Resonance Energy Transfer‐Enhanced Photothermal Therapy

Stimuli‐responsive anticancer agents are of particular interest in the field of cancer therapy. Nevertheless, so far stimuli‐responsive photothermal agents have been explored with limited success for cancer photothermal therapy (PTT). In this work, as a proof‐of‐concept, a pH‐responsive photothermal nanoconjugate for enhanced PTT efficacy, in which graphene oxide (GO) with broad NIR absorbance and effective photothermal conversion efficiency is selected as a typical model receptor of fluorescence resonance energy transfer (FRET), and grafted cyanine dye (e.g., Cypate) acts as the donor of near‐infrared fluorescence (NIRF), is reported for the first time. The conjugate of Cypate‐grafted GO exhibits different conformations in aqueous solutions at various pH, which can trigger pH‐dependent FRET effect between GO and Cypate and thus induce pH‐responsive photothermal effect of GO‐Cypate. GO‐Cypate exhibits severe cell damage owing to the enhanced photothermal effect in lysosomes, and thus generate synergistic PTT efficacy with tumor ablation upon photoirradiation after a single‐dose intravenous injection. The photothermal nanoconjugate with broad NIR absorbance as the effective receptor of FRET can smartly convert emitted NIRF energy from donor cyanine dye into additional photothermal effect for improving PTT. These results suggest that the smart nanoconjugate can act as a promising stimuli‐responsive photothermal nanoplatform for cancer therapy.     

Smart Anisotropic Wetting Surfaces with Reversed pH‐Responsive Wetting Directions

Smart pH‐responsive surfaces that could autonomously induce unidirectional wetting of acid and base with reversed directions are fabricated. The smart surfaces, consisting of chemistry‐asymmetric “Janus” silicon cylinder arrays (Si‐CAs), are prepared by precise modification of functional groups on each cylinder unit. Herein, amino and carboxyl groups are chosen as typical pH‐responsive groups, owing to their protonation/deprotonation effect in response to pH of the contacted aqueous solution. One side of the Si‐CAs is modified by poly(2‐(dimethylamino)ethyl methacrylate), while the other side is modified by mixed self‐assembled monolayers of 1‐dodecanethiol and 11‐mercaptoundecanoic acid. On such surfaces, it is observed that acid and base wet in a unidirectional manner toward corresponding directions that are modified by amino or carboxyl groups, which is caused by asynchronous change of wetting property on two sides of the asymmetric structures. The as‐prepared Janus surfaces could regulate the wetting behavior of acid and base and could direct unidirectional wetting of water with reversed directions when the surfaces are treated by strong acid or base. Due to the excellent response capability, the smart surfaces are potential candidates to be applied in sensors, microfluidics, oil/water separation, and smart interfacial design.     

pH‐ and NIR Light‐Responsive Micelles with Hyperthermia‐Triggered Tumor Penetration and Cytoplasm Drug Release to Reverse Doxorubicin Resistance in Breast Cancer

The acquisition of multidrug resistance (MDR) is a major hurdle for the successful chemotherapy of tumors. Herein, a novel hybrid micelle with pH and near‐infrared (NIR) light dual‐responsive property is reported for reversing doxorubicin (DOX) resistance in breast cancer. The hybrid micelles are designed to integrate the pH‐ and NIR light‐responsive property of an amphiphilic diblock polymer and the high DOX loading capacity of a polymeric prodrug into one single nanocomposite. At physiological condition (i.e., pH 7.4), the micelles form compact nanostructure with particle size around 30 nm to facilitate blood circulation and passive tumor targeting. Meanwhile, the micelles are quickly dissociated in weakly acidic environment (i.e., pH ≤ 6.2) to release DOX prodrug. When exposed to NIR laser irradiation, the hybrid micelles can trigger notable tumor penetration and cytosol release of DOX payload by inducing tunable hyperthermia effect. In combination with localized NIR laser irradiation, the hybrid micelles significantly inhibit the growth of DOX‐resistant MCF‐7/ADR breast cancer in an orthotopic tumor bearing mouse model. Taken together, this pH and NIR light‐responsive micelles with hyperthermia‐triggered tumor penetration and cytoplasm drug release can be an effective nanoplatform to combat cancer MDR.     

Multifunctional Up‐Converting Nanocomposites with Smart Polymer Brushes Gated Mesopores for Cell Imaging and Thermo/pH Dual‐Responsive Drug Controlled Release

Multifunctional nanocarriers based on the up‐conversion luminescent nanoparticles of NaYF₄:Yb³⁺/Er³⁺ core (UCNPs) and thermo/pH‐coupling sensitive polymer poly[(N‐isopropylacrylamide)‐co‐(methacrylic acid)] (P(NIPAm‐co‐MAA)) gated mesoporous silica shell are reported for cancer theranostics, including fluorescence imaging, and for controlled drug release for therapy. The as‐synthesized hybrid nanospheres UCNPs@mSiO₂‐P(NIPAm‐co‐MAA) show bright green up‐conversion fluorescence under 980 nm laser excitation and the thermo/pH‐sensitive polymer is active as a “valve” to moderate the diffusion of the embedded drugs in‐and‐out of the pore channels of the silica container. The anticancer drug doxorubicin hydrochloride (DOX) can be absorbed into UCNPs@mSiO₂‐P(NIPAm‐co‐MAA) nanospheres and the composite drug delivery system (DDS) shows a low level of leakage at low temperature/high pH values but significantly enhanced release at higher temperature/lower pH values, exhibiting an apparent thermo/pH controlled “on‐off” drug release pattern. The as‐prepared UCNPs@mSiO₂‐P(NIPAm‐co‐MAA) hybrid nanospheres can be used as bioimaging agents and biomonitors to track the extent of drug release. The reported multifunctional nanocarriers represent a novel and versatile class of platform for simultaneous imaging and stimuli‐responsive controlled drug delivery.     

pH‐Responsive,Light‐Triggered on‐Demand Antibiotic Release from Functional Metal–Organic Framework for Bacterial Infection Combination Therapy

To satisfy the ever‐growing demand in bacterial infection therapy and other fields of science, great effort is being devoted to the development of methods to precisely control drug release and achieve targeted use of an active substance at the right time and place. Here, a new strategy for bacterial infection combination therapy based on the light‐responsive zeolitic imidazolate framework (ZIF) is reported. A pH‐jump reagent is modified into the porous structure of ZIF nanoparticles as a gatekeeper, allowing the UV‐light (365 nm) responsive in situ production of acid, which subsequently induces pH‐dependent degradation of ZIF and promotes the release of the antibiotic loaded in the mesopores. The combination of the UV‐light, the pH‐triggered precise antibiotic release, and the zinc ions enables the light‐activated nanocomposite to significantly inhibit bacteria‐induced wound infection and accelerate wound healing, indicating a switchable and synergistic antibacterial effect. The light irradiated accumulation of acid ensures the controlled release of antibiotic and controlled degradation of ZIF, suggesting the therapeutic potential of the metal–organic frameworks‐based smart platform for controlling bacterial infection.     

Layer‐by‐Layer Assembly of Light‐Responsive Polymeric Multilayer Systems

Layer‐by‐Layer (LbL) assembly is a simple and highly versatile method to modify surfaces and fabricate robust and highly‐ordered nanostructured coatings over almost any type of substrate. Such versatility enables the incorporation of a plethora of building blocks, including materials exhibiting switchable properties, in a single device through a multitude of complementary intermolecular interactions. Switchable materials may undergo reversible physicochemical changes in response to a variety of external triggers. Although most of the works in the literature have been focusing on stimuli‐responsive materials that are sensitive to common triggers such as pH, ionic strength, or temperature, much less has been discussed on LbL systems which are sensitive to non‐invasive and easily controlled light stimulus, despite its unique potential. This review provides a deep overview of the recent progresses achieved in the design and fabrication of light‐responsive LbL polymeric multilayer systems, their potential future challenges and opportunities, and possible applications. Many examples are given on light‐responsive polymeric multilayer assemblies built from metal nanoparticles, functional dyes, and metal oxides. Such stimuli‐responsive functional materials, and combinations among them, may lead to novel and highly promising nanostructured smart functional systems well‐suited for a wide range of research fields, including biomedicine and biotechnology.     

Remotely Controlled Red Blood Cell Carriers for Cancer Targeting and Near‐Infrared Light‐Triggered Drug Release in Combined Photothermal–Chemotherapy

Red blood cells (RBCs), the “innate carriers” in blood vessels, are gifted with many unique advantages in drug transportation over synthetic drug delivery systems (DDSs). Herein, a tumor angiogenesis targeting, light stimulus‐responsive, RBC‐based DDS is developed by incorporating various functional components within the RBC platform. An albumin bound near‐infrared (NIR) dye, together with a chemotherapy drug doxorubicin, is encapsulated inside RBCs, the surfaces of which are modified with a targeting peptide to allow cancer targeting. Under stimulation by an external NIR laser, the membrane of the RBCs would be destroyed by the light‐induced photothermal heating, resulting in effective drug release. As a proof of principle, RBC‐based cancer cell targeted drug delivery and light‐controlled drug release is demonstrated in vitro, achieving a marked synergistic therapeutic effect through the combined photothermal–chemotherapy. This work presents a novel design of smart RBC carriers, which are inherently biocompatible, promising for targeted combination therapy of cancer.     

Stimuli‐Responsive Hybridized Nanostructures

Through innovative nanosynthesis techniques and advanced surface‐passivation methods, diversified luminescent nanocrystals, like quantum dots, metal nanoclusters, carbon dots, and upconversion nanoparticles, are produced successfully to exhibit greatly improved performance in various applications, due to their color tunability and resistance to photobleaching. Their further hybridization with stimuli‐responsive polymers endows the resultant nanohybrids with unique smart functions, which can reversibly respond to external stimuli or environmental changes via alternation in luminescence. Due to their multifunctional properties, these responsive luminescent nanohybrids are attracting more and more interest in foundation research and promising applications recently. Here, important developments and achievements made in this emerging field are summarized to highlight the integration concepts and fabrication methods for luminescent nanohybrids, and their special responsive functions to temperature, pH, fields, and analytes. At the same time, their smart applications are also overviewed for demonstrating novel actions of responsive nanohybrids via various intelligent operations. The aim is to understand and accelerate more advanced developments in creating varied and intelligent nanosystems, and provide perspectives to promote a further revolution of smart materials and technology.     

Touch‐Interactive Flexible Sustainable Energy Harvester and Self‐Powered Smart Card

Sustainable and safe energy sources combined with cost effectiveness are major goals for society when considering the current scenario of mass production of portable and Internet of Things (IoT) devices along with the huge amount of inevitable e‐waste. The conceptual design of a self‐powered “eco‐energy” smart card based on paper promotes green and clean energy, which will bring the zero e‐waste challenge one step closer to fruition. A commercial raw filter paper is modified through a fast in situ functionalization method, resulting in a conductive cellulose fiber/polyaniline composite, which is then applied as an energy harvester based on a mechano‐responsive charge transfer mechanism through a metal/conducting polymer interface. Different electrodes are studied to optimize charge transfer based on contact energy level differences. The highest power density and current density obtained from such a paper‐based “eco‐energy” smart card device are 1.75 W m^?2 and 33.5 mA m^?2 respectively. This self‐powered smart energy card is also able to light up several commercial light‐emitting diodes, power on electronic devices, and charge capacitors.     

Protein/Polymer‐Based Dual‐Responsive Gold Nanoparticles with pH‐Dependent Thermal Sensitivity

This article presents the synthesis and physicochemical behavior of dual‐responsive plasmonic nanoparticles with reversible optical properties based on protein‐coated gold nanoparticles grafted with thermosensitive polymer brushes by means of surface‐initiated atom transfer radical polymerization (SI‐ATRP) that exhibit pH‐dependent thermo‐responsive behavior. Spherical gold NPs of two different sizes (15 nm and 60 nm) and with different stabilizing agents (citrate and cetyltrimethylammonium bromide (CTAB), respectively) were first capped with bovine serum albumin (BSA). The resulting BSA‐capped NPs (Au@BSA NPs) exhibited not only extremely high colloidal stability under physiological conditions, but also a reversible U‐shaped pH‐responsive behavior, similar to pure BSA. The ?‐amine of the L‐lysine in the protein coating was then used to covalently bind an ATRP‐initiator, allowing for the SI‐ATRP of thermosensitive polymer brushes of oligo(ethylene glycol) methacrylates with an LCST of 42 °C in pure water and around 37 °C under physiological conditions. Such protein coated nanoparticles grafted with thermosensitive polymers exhibit a smart pH‐dependent thermosensitive behavior.     

Stimuli‐Responsive Liquid Marbles: Controlling Structure,Shape, Stability,and Motion

“Liquid marbles” are liquid‐in‐gas dispersed systems stabilized by hydrophobic solid particles adsorbed at the gas‐liquid interface. The structure, stability and movement of these liquid marbles can be controlled by external stimuli such as pH, temperature, light, magnetic and electric fields, ultrasonic, mechanical stress and organic solvents. Stimuli‐responsive modes can be categorized into five classes: (i) liquid marbles whose stability can be controlled by adsorption/desorption of solid particles to/from liquid surfaces, (ii) liquid marbles that can open and close their particle‐coated surface by moving particles to and from the gas‐liquid surface, (iii) liquid marbles that can move, (iv) liquid marbles that can change their shape and (v) liquid marbles that can be split. As a result of these stimuli‐responsive characteristics, liquid marbles offer potential in the areas of controlled encapsulation, delivery and release.