Multistimuli-responsive fluorescence behaviours of aggregation-induced emission small-molecule and electrospun nanofibre films for acid–base vapour sensing

Multistimuli-responsive fluorescent materials have garnered great research interest benefited from their practical applications. Two twisted-structure compounds containing tetraphenylethylene (TPE) as the aggregation-induced emission (AIE) group and a pyridine unit as the acid reaction site to obtain new multistimuli-responsive fluorescent compounds (namely, TPECNPy: TPECNPy-2 and TPECNPy-3) were successfully synthesized through a one-step Knoevenagel condensation reaction. The multiple-stimuli response process of TPECNPy was investigated by means of photoluminescence (PL) spectra and emission colour. The results showed that both TPECNPy compounds with excellent AIE abilities displayed reversible emission wavelength and colour changes in response to multiple external stimuli, including grinding–fuming by CH₂Cl₂ or annealing and HCl-NH₃ vapour fuming. More importantly, fluorescent nanofibre films were prepared by electrospinning a solution of TPECNPy mixed with cellulose acetate (CA), and these exhibited reversible acid-induced discolouration, even with only 1 wt% TPECNPy. The results of this study may inspire strategies for designing multistimuli-responsive materials and preparing fluorescent sensing nanofibre films.     

Metal-free click and bioorthogonal reactions of aggregation-induced emission probes for lighting up living systems

In 2002, two transformative research paradigms emerged: ‘click chemistry’ and ‘aggregation-induced emission (AIE),’ both leaving significant impacts on early 21st-century academia. Click chemistry, which describes the straightforward and reliable reactions for linking two building blocks, has simplified complex molecular syntheses and functionalization, propelling advancements in polymer, material, and life science. In particular, nontoxic, metal-free click reactions involving abiotic functional groups have matured into bioorthogonal reactions. These are organic ligations capable of selective and efficient operations even in congested living systems, therefore enabling in vitro to in vivo biomolecular labelling. Concurrently, AIE, a fluorogenic phenomenon of twisted π-conjugated compounds upon aggregation, has offered profound insight into solid-state photophysics and promoted the creation of aggregate materials. The inherent fluorogenicity and aggregate-emission properties of AIE luminogens have found extensive application in biological imaging, characterized by their high-contrast and photostable fluorescent signals. As such, the convergence of these two domains to yield efficient labelling with excellent fluorescence images is an anticipated progression in recent life science research. In this review, we intend to showcase the synergetic applications of AIE probes and metal-free click or bioorthogonal reactions, highlighting both the achievements and the unexplored avenues in this promising field.     

The Biological Applications of Two Aggregation‐Induced Emission Luminogens

Fluorescence imaging, as a commonly used scientific tool, is widely applied in various biomedical and material structures through visualization technology. Highly selective and sensitive luminescent biological probes, as well as those with good water solubility, are urgently needed for biomedical research. In contrast to the traditional aggregation‐caused quenching of fluorescence, in the unique phenomenon of aggregation‐induced emission (AIE), the individual luminogens have extremely weak or no emissivity because they each have free intramolecular motion; however, when they form aggregates, these components immediately “light up”. Since the discovery of “turn‐on” mechanism, researchers have been studying and applying AIE in a variety of fields to develop more sensitive, selective, and efficient strategies for the AIE dyes. There are numerous advantages to the use of AIE‐based methods, including low background interference, strong contrast, high performance in intracellular imaging, and the ability for long‐term monitoring in vivo. In this review, two typical examples of AIEgens, TPE‐Cy and TPE‐Ph‐In, are described, including their structure properties and applications. Recent progress in the biological applications is mainly focused on. Undoubtedly, in the near future, an increasing number of encouraging and practical ideas will promote the development of more AIEgens for broad use in biomedical applications.     

A new strategy of transforming an ACQ compound into an AIE theranostic system for bacterial imaging and photodynamic antibacterial therapy

An organic chemical with fluorescence quenching properties [aggregation-caused quenching (ACQ)] may often be transformed by adding functional groups that cause aggregation-induced emission (AIE) to its molecular scaffold. Such structural change techniques, however, sometimes require challenging chemical reactions. SF136 is a type of chalcone, and it is an typical ACQ organic compound. In this study, cationic surfactants like hexadecyltrimethylammonium bromide (CTAB) and polyethyleneimine (PEI) were used to convert the ACQ compound SF136 into an AIE compound without adding any AIE structure units. In comparison to SF136, the SF136-CTAB NPS system not only demonstrated improved bacterial fluorescence imaging capabilities, but also increased photodynamic antibacterial activity, which is connected to its improved targeting and reactive oxygen species (ROS) production abilities. It is a promising theranostic substance against bacteria owing to these enhanced qualities. Other ACQ fluorescent compounds may also benefit from using this approach, broadening the scope of their potential applications.     

Synthesis and chiroptical properties of chiral azoaromatic dendrimers with a C3‐symmetrical core

New chiral azoaromatic dendrimeric systems have been synthesized starting from 1,3,5‐benzenetricarbonyl trichloride as the core molecule. The simultaneous presence of the (S)‐3‐hydroxy pyrrolidinyl ring as the optically active moiety and the azobenzene donor‐acceptor conjugated system as the photochromic group with permanent dipole moment, makes these systems potentially interesting as materials for advanced applications in nanotechnologies. All the compounds obtained have been characterized with particular attention to the effects induced by changing the electron‐withdrawing group in the chromophoric moiety and to their optical activity. A strong nonlinear enhancement of chiroptical properties related to the number of chiral units linked to the symmetrical core is observed in these derivatives, which indicates the presence of conformationally chiral substructures. Chirality, 2010. © 2009 Wiley‐Liss, Inc.     

In situ localization of alkaline phosphatase activity in tumor cells by an aggregation-induced emission fluorophore-based probes

In situ detection of certain specific enzyme activities in cells is deeply attached to tumor diagnosis. Conventional enzyme-responsive fluorescent probes have difficulty detecting targeted enzymes in situ in cells due to the low detection accuracy caused by the spread of fluorescence probes. In order to solve this problem, we have designed and synthesized an enzyme-responsive, water-soluble fluorescent probe with AIE characteristics, which could aggregate and precipitate to produce in situ fluorescence when reacting with the targeted enzyme in cells. The AIE fluorophore (TPEQH) was utilized to design the enzyme-responsive, fluorescent probe (TPEQHA) by introducing a phosphate group on to it, which could be specifically decomposed by the targeted enzyme, namely alkaline phosphatase (ALP). In tumor cells, TPEQH was highly produced due to the interaction of phosphate on the TPEQHA and the overexpressed ALP. Water-insoluble TPEQH then precipitated and release fluorescence in situ, thereby successfully detecting the ALP. Furthermore, the expression level of ALP could be determined by the fluorescence intensity of TPEQH with higher accuracy due to the inhibition of TPEQH leak, which demonstrated a potential application of in suit ALP detection in both clinical diagnosis and scientific research of tumor.     

Anti-allergic effects of Artemisia iwayomogi on mast cell-mediated allergy model

The discovery of drugs for the treatment of allergic disease is an important subject in human health. The Artemisia iwayomogi (Compositae) (AIE) has been used as a traditional medicine in Korea and is known to have an anti-inflammatory effect. However, its specific mechanism of action is still unknown. In this report, we investigated the effect of AIE on the mast cell-mediated allergy model and studied the possible mechanism of action. AIE inhibited compound 48/80-induced systemic reactions and plasma histamine release in mice. AIE decreased immunoglobulin E (IgE)-mediated local allergic reaction, passive cutaneous anaphylaxis (PCA) reaction. AIE dose dependently attenuated histamine release from rat peritoneal mast cells activated by compound 48/80 or IgE. AIE decreased the compound 48/80-induced intracellular Ca(2+). Furthermore, AIE decreased the phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187-stimulated tumor necrosis factor-alpha and interleukin-6 gene expression and production in human mast cells. The inhibitory effect of AIE on the proinflammatory cytokine was p38 mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-kappaB) dependent. AIE attenuated PMA plus A23187-induced degradation of IkappaBalpha and nuclear translocation of NF-kappaB and specifically blocked activation of p38 MAPK but not that of c-jun N-terminal kinase and extracellular signal-regulated kinase. Our findings provide evidence that AIE inhibits mast cell-derived immediate-type allergic reactions and involvement of intracellular Ca(2+), proinflammatory cytokines, p38 MAPK, and NF-kappaB in these effects.     

Modern fluorescent proteins: from chromophore formation to novel intracellular applications

The diverse biochemical and photophysical properties of fluorescent proteins (FPs) have enabled the generation of a growing palette of colors, providing unique opportunities for their use in a variety of modern biology applications. Modulation of these FP characteristics is achieved through diversity in both the structure of the chromophore as well as the contacts between the chromophore and the surrounding protein barrel. Here we review our current knowledge of blue, green, and red chromophore formation in permanently emitting FPs, photoactivatable FPs, and fluorescent timers. Progress in understanding the interplay between FP structure and function has allowed the engineering of FPs with many desirable features, and enabled recent advances in microscopy techniques such as super-resolution imaging of single molecules, imaging of protein dynamics, photochromic FRET, deep-tissue imaging, and multicolor two-photon microscopy in live animals.     

Dual-mode security authentication of SrAl2O4:Eu,Dy phosphor encapsulated in electrospun cellulose acetate nanofibrous films

Photochromic inks have been an attractive authentication strategy to improve the anti-counterfeiting efficiency of commercial products. However, recent reports have shown significant disadvantages with photochromic inks, including poor durability and high cost. In this context, we developed novel photochromic nanofibres for advanced anti-counterfeiting applications. Lanthanide-doped strontium aluminate (LdSA) nanoparticles (NPs) were prepared and immobilized into electrospun cellulose acetate nanofibres (CANF). Authentication materials immobilized with inorganic photochromic agents can warranty durability and photostability. Therefore, the ultraviolet-stimulated photochromism of LdSA-encapsulated cellulose acetate nanofibres (LdSA@CANF) demonstrated high reversibility and photostability. A broad range of cellulose acetate nanofibres with unique emission characteristics was developed when applying different ratios of LdSA NPs. LdSA@CANF appeared colourless under visible daylight, whereas a green emission was monitored under ultraviolet-light illumination. The shape and chemical content of the photochromic fibrous films were examined using various analytical techniques. The mechanical characteristics of LdSA@CANF-coated paper were investigated. The emission wavelength was detected at 514 nm to designate green colour, whereas the excitation wavelength was detected at 369 nm to indicate transparency. The prepared cellulose acetate nanofibrous film can be described as an efficient strategy for the anti-counterfeiting of commercialized items.     

Reversible photoswitching in fluorescent proteins: a mechanistic view

Phototransformable fluorescent proteins (FPs) have received considerable attention in recent years, because they enable many new exciting modalities in fluorescence microscopy and biotechnology. On illumination with proper actinic light, phototransformable FPs are amenable to long-lived transitions between various fluorescent or nonfluorescent states, resulting in processes known as photoactivation, photoconversion, or photoswitching. Here, we review the subclass of photoswitchable FPs with a mechanistic perspective. These proteins offer the widest range of practical applications, including reversible high-density data bio-storage, photochromic FRET, and super-resolution microscopy by either point-scanning, structured illumination, or single molecule-based wide-field approaches. Photoswitching can be engineered to occur with high contrast in both Hydrozoan and Anthozoan FPs and typically results from a combination of chromophore cis-trans isomerization and protonation change. However, other switching schemes based on, for example, chromophore hydration/dehydration have been discovered, and it seems clear that ever more performant variants will be developed in the future.     

Bacteriorhodopsin: mutating a biomaterial into an optoelectronic material

Bacteriorhodopsin (BR) is the key protein for the halobacterial photosynthetic capabilities and is one of the very rare molecules which occur in crystalline form in nature. Since its discovery, which was reported in 1971, many efforts have been made to exploit the obvious technical potential of this molecule. Successful application of gene technology methods for the modification of the physical function of a biomolecule was first demonstrated with BR. This approach points the way to a new class of materials derived from evolutionary optimized biomaterials by genetic re-engineering. Mutated BRs proved to have significant advantages over the wild type in optical applications. The current status of potential technical applications of BR is reviewed. BR is employed as a photoelectric, photochromic or energy-converting element. First systems now exist which demonstrate the successful integration of this new material into existing technologies. Analyzing the patents filed, which claim the processing or application of BR, gives an indication to areas where further technical uses are to be expected in the near future. Received: 16 November 1999 / Received revision: 3 December 1999 / Accepted: 3 December 1999     

Sonoproduction of liposomes and protein particles as templates for delivery purposes

The development of nano and micro delivery systems (DS), so small in size, is growing in importance, such as in drug targeting. In an era where nano is the new trend, micro and nano materials are in the forefront of progress. These systems can be produced by a diversity of methods. However, the use of high-intensity ultrasound offers an easy and versatile tool for nano- and microstructured materials that are often unavailable by conventional methods. Similarly to the synthesis methods that can be used, several starting materials can be applied to produce particulate systems. In this review, the recent strategic development of DS is discussed with emphasis on liposomes and polymer-based, specially protein-based, nanomedicine platforms for drug delivery. Among the variety of applications that materials in the particulate form can have, the control release of drugs is probably the most prominent one, as these have been in the forefront line of interest for biomedical applications. The basic concepts of sonochemical process pertaining to DS are summarized as well as the role of sonochemical procedure to their preparation. The different applications of these systems wrap up this review.     

Self-assembled monolayers and polymer brushes in biotechnology: current applications and future perspectives

The chemistry and topography of a surface affect biological response and are of fundamental importance, especially when living systems encounter synthetic surfaces. Most biomolecules have immense recognition power (specific binding) and simultaneously have a tendency to physically adsorb onto a solid substrate without specific receptor recognition (nonspecific adsorption). Therefore, to create useful materials for many biotechnology applications, interfaces are required that have both enhanced specific binding and reduced nonspecific binding. Thus, in applications such as sensors, the tailoring of surface chemistry and the use of micro or nanofabrication techniques becomes an important avenue for the production of surfaces with specific binding properties and minimal background interference. Both self-assembled monolayers (SAMs) and polymer brushes have attracted considerable attention as surface-active materials. In this review, we discuss both of these materials with their potential applications in biotechnology. We also summarize lithographic methods for pattern formation using combined top-down and bottom-up approaches and briefly discuss the future of these materials by describing emerging new applications.     

Viral vectors for production of recombinant proteins in plants

Global demand for recombinant proteins has steadily accelerated for the last 20 years. These recombinant proteins have a wide range of important applications, including vaccines and therapeutics for human and animal health, industrial enzymes, new materials and components of novel nano-particles for various applications. The majority of recombinant proteins are produced by traditional biological "factories," that is, predominantly mammalian and microbial cell cultures along with yeast and insect cells. However, these traditional technologies cannot satisfy the increasing market demand due to prohibitive capital investment requirements. During the last two decades, plants have been under intensive investigation to provide an alternative system for cost-effective, highly scalable, and safe production of recombinant proteins. Although the genetic engineering of plant viral vectors for heterologous gene expression can be dated back to the early 1980s, recent understanding of plant virology and technical progress in molecular biology have allowed for significant improvements and fine tuning of these vectors. These breakthroughs enable the flourishing of a variety of new viral-based expression systems and their wide application by academic and industry groups. In this review, we describe the principal plant viral-based production strategies and the latest plant viral expression systems, with a particular focus on the variety of proteins produced and their applications. We will summarize the recent progress in the downstream processing of plant materials for efficient extraction and purification of recombinant proteins.     

Designing Silk-silk Protein Alloy Materials for Biomedical Applications

Fibrous proteins display different sequences and structures that have been used for various applications in biomedical fields such as biosensors, nanomedicine, tissue regeneration, and drug delivery. Designing materials based on the molecular-scale interactions between these proteins will help generate new multifunctional protein alloy biomaterials with tunable properties. Such alloy material systems also provide advantages in comparison to traditional synthetic polymers due to the materials biodegradability, biocompatibility, and tenability in the body. This article used the protein blends of wild tussah silk (Antheraea pernyi) and domestic mulberry silk (Bombyx mori) as an example to provide useful protocols regarding these topics, including how to predict protein-protein interactions by computational methods, how to produce protein alloy solutions, how to verify alloy systems by thermal analysis, and how to fabricate variable alloy materials including optical materials with diffraction gratings, electric materials with circuits coatings, and pharmaceutical materials for drug release and delivery. These methods can provide important information for designing the next generation multifunctional biomaterials based on different protein alloys.     

Photoactivatable aggregation-induced emission luminogens based on photodehydrogenation reactions for biomedical applications

The development of photoactivatable aggregation-induced emission (AIE) probes is one of the hotspots for bioimaging and imaging-guided precise disease therapy due to the distinct advantages of high spatiotemporal resolution, precise spatiotemporal controllability, and noninvasiveness of light. To design and develop novel photoactivatable AIE probes, functional groups based on photodehydrogenation reaction mechanisms are combined with the AIE-active skeleton. Here, the recent progress in biomedical applications of photoactivatable AIE probes based on photocyclodehydrogenation and photo-oxidative dehydrogenation reactions are summarized briefly. Moreover, the outlook for photoactivatable AIE probes is discussed to aim at promoting innovative research in biomedical applications.     

Electroactive polymer actuators as artificial muscles: are they ready for bioinspired applications?

Electroactive polymer (EAP) actuators are electrically responsive materials that have several characteristics in common with natural muscles. Thus, they are being studied as 'artificial muscles' for a variety of biomimetic motion applications. EAP materials are commonly classified into two major families: ionic EAPs, activated by an electrically induced transport of ions and/or solvent, and electronic EAPs, activated by electrostatic forces. Although several EAP materials and their properties have been known for many decades, they have found very limited applications. Such a trend has changed recently as a result of an effective synergy of at least three main factors: key scientific breakthroughs being achieved in some of the existing EAP technologies; unprecedented electromechanical properties being discovered in materials previously developed for different purposes; and higher concentration of efforts for industrial exploitation. As an outcome, after several years of basic research, today the EAP field is just starting to undergo transition from academia into commercialization, with significant investments from large companies. This paper presents a brief overview on the full range of EAP actuator types and the most significant areas of interest for applications. It is hoped that this overview can instruct the reader on how EAPs can enable bioinspired motion systems.     

FAST slides: a novel surface for microarrays

We have evaluated FAST slides, a glass slide with a microporous polymeric surface that is a suitable substrate for microarray technology. The surface is a nitrocellulose-based polymer that binds DNA and proteins in a noncovalent but irreversible manner. FAST slides are compatible with robotic systems currently used to create microarrays and can easily accommodate volumes of 0.03-2 nL/spot. Our data indicate that FAST slides have a much higher binding capacity for DNA and better spot-to-spot consistency than traditional poly-lysine-coated slides. In addition, FAST slides are well suited for fluorescent detection because of their relatively low light scatter and efficient retention of arrayed DNA. These properties translate into fluorescent sensitivity comparable to modified glass surfaces. FAST slides are also ideal for arraying proteins, making them the only substrate of their kind currently available for microarray applications.     

Simple preparation of novel photochromic polyvinyl alcohol/carboxymethyl cellulose security barcode incorporated with lanthanide-doped aluminate for anticounterfeiting applications

Forgery and low-quality products pose a danger to society. Therefore, there are increasing demands for the production of easy-to-recognize and difficult-to-copy anticounterfeiting materials. Products with smart photochromic and fluorescence properties can change colour and emission spectra responding to a light source. In this context, we devised a straightforward preparation of a luminescent polyvinyl alcohol/carboxymethyl cellulose (PVA/CMC) nanocomposite to function as a transparent labelling film. The lanthanide-doped aluminate (LdA) was prepared in the nanoparticle form to indicate diameters of 35–115 nm. Different ratios of the LdA were physically dispersed in the PVA/CMC nanocomposite label film to provide photochromic, ultraviolet protection, antimicrobial activity, and hydrophobic properties. Fluorescence peaks were detected at 365 and 519 nm to indicate a colour change to green. As a result of increasing the phosphor ratio, improved superhydrophobic activity was achieved as the contact angle was increased from 126.1° to 146.0° without affecting the film's original physical and mechanical properties. Both ultraviolet (UV) light protection and antibacterial activity were also investigated. The films showed a quick and reversible photochromic response without fatigue. The current strategy reported the development of a photochromic smart label that is transparent, cost effective, and flexible. As a result, numerous anticounterfeiting products can benefit from the current label for a better market. LdA-loaded PVA/CMC films demonstrated antibacterial activity between poor, good, very good, and outstanding as the percentage of LdA in the film matrix increased. The current film can be applied as a transparent photochromic security barcode for anticounterfeiting applications and smart packaging.     

Design and synthesis of efficient fluorescent dyes for incorporation into DNA backbone and biomolecule detection

We report here the design and synthesis of a series of pi-conjugated fluorescent dyes with D-A-D (D, donor; A, acceptor), D-pi-D, A-pi-A, and D-pi-A for applications as the signaling motif in biological-synthetic hybrid foldamers for DNA detection. The Horner-Wadsworth-Emmons (HWE) reaction and Knoevenagel condensation were demonstrated as the optimum ways for construction of long pi-conjugated systems. Such rodlike chromophores have distinct advantages, as their fluorescence properties are not quenched by the presence of DNA. To be incorporated into the backbone of DNA, the chromophores need to be reasonably soluble in organic solvent for solid-phase synthesis, and therefore a strategy of using flexible tetraethylene glycol (TEG) linkers at either end of these rodlike dyes was developed. The presence of TEG facilitates the protection of the chain-growing hydroxyl group with DMTrCl (dimethoxytrityl chloride) as well as the activation of the coupling step with phosphoramidite chemistry on an automated DNA synthesizer. To form fluorescence resonance energy transfer (FRET) pairs, six synthetic chromophores with blue to red fluorescence have been developed, and those with orthogonal fluorescent emission were chosen for incorporation into DNA-chromophore hybrid foldamers.