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Novel BODIPY photosensitizers were developed for imaging-guided photodynamic therapy. The introduction of a strong electron donor to the BODIPY core through a phenyl linker combined with the twisted arrangement between the donor and the BODIPY acceptor is essential for reducing the energy gap between the lowest singlet excited state and the lowest triplet state (ΔEST ), leading to a significant enhancement in the intersystem crossing (ISC) of the BODIPYs. Remarkably, the BDP-5 with the smallest ΔEST (ca. 0.44 eV) exhibited excellent singlet oxygen generation capabilities in both organic and aqueous solutions. BDP-5 also displayed bright emission in the far-red/near-infrared region in the condensed states. More importantly, both in vitro and in vivo studies demonstrated that BDP-5 NPs displayed a high potential for photodynamic cancer therapy and bioimaging.

Phototheranostic nanoplatforms are of particular interest for cancer diagnosis and imaging-guided therapy. Herein, we develop a supramolecular approach to fabricate a nanostructured phototheranostic agent through the direct self-assembly of two water-soluble phthalocyanine derivatives, PcS4 and PcN4. The nature of the molecular recognition between PcS4 and PcN4 facilitates the formation of nanostructure (PcS4-PcN4) and consequently enables the fabrication of PcS4-PcN4 with completely quenched fluorescence and reduced singlet oxygen generation, leading to the high photoacoustic and photothermal activity of PcS4-PcN4. In vivo evaluations suggest that PcS4-PcN4 could not only efficiently visualize a tumor with high contrast through whole-body photoacoustic imaging but also enable excellent photothermal therapy for cancer.

Monitoring fluctuations in enzyme overexpression facilitates early tumor detection and excision. An AIEgen probe (DQM-ALP) for the imaging of alkaline phosphatase (ALP) activity was synthesized. The probe consists of a quinoline-malononitrile (QM) core decorated with hydrophilic phosphate groups as ALP-recognition units. The rapid liberation of DQM-OH aggregates in the presence of ALP resulted in aggregation-induced fluorescence. The up-regulation of ALP expression in tumor cells was imaged using DQM-ALP. The probe permeated into 3D cervical and liver tumor spheroids for imaging spatially heterogeneous ALP activity with high spatial resolution on a two-photon microscopy platform, providing the fluorescence-guided recognition of sub-millimeter tumorigenesis. DQM-ALP enabled differentiation between tumor and normal tissue ex vivo and in vivo, suggesting that the probe may serve as a powerful tool to assist surgeons during tumor resection.

With the ever-increasing threat posed by the multi-drug resistance of bacteria, the development of non-antibiotic agents for the broad-spectrum eradication of clinically prevalent superbugs remains a global challenge. Here, we demonstrate the simple supramolecular self-assembly of structurally defined graphene nanoribbons (GNRs) with a cationic porphyrin (Pp4N) to afford unique one-dimensional wire-like GNR superstructures coated with Pp4N nanoparticles. This Pp4N/GNR nanocomposite displays excellent dual-modal properties with significant reactive-oxygen-species (ROS) production (in photodynamic therapy) and temperature elevation (in photothermal therapy) upon light irradiation at 660 and 808 nm, respectively. This combined approach proved synergistic, providing an impressive antimicrobial effect that led to the complete annihilation of a wide spectrum of Gram-positive, Gram-negative, and drug-resistant bacteria both in vitro and in vivo. The study also unveils the promise of GNRs as a new platform to develop dual-modal antimicrobial agents that are able to overcome antibiotic resistance.

Revealing the structural evolution mechanisms of supramolecular self-assembly can facilitate the exploitation of new self-assembly pathways and various functional materials. Here, this work reports a unique intramolecular rotation-induced structural evolution of supramolecular assemblies from a metastable state to a thermodynamically stable state using a twisting D-A molecule. These self-assemblies are applied to the signal differentiation detection of toxic dimethylsulfide (DMS) vapors. The F

Activity‐based approaches for designing AIEgens possess prominent advantages including high selectivity, sensitivity, and signal‐to‐noise ratio, and they have received more attention in recent years. Excellent activatable AIE probes have been reported for detecting toxic substances, imaging intracellular active molecules/biomolecules, as well as monitoring the activity of overexpressed enzymes in cancers. Moreover, the majority of activatable theranostic AIEgens can be specifically triggered in cancer cells and can kill these cells under light irradiation, while they have no distinct effect on normal cells, demonstrating satisfactory therapeutic selectivity that is superior to that of traditional chemotherapy. Thus, in this review, we systematically summarized the development of activatable AIE bioprobes in recent years from molecular design principles to biological applications. The challenges of activatable AIE probes and the corresponding solutions are described. We hope that the information provided in this review will facilitate the design of more activatable AIE probes to promote practical application of corresponding AIEgens.

In this investigation, a new terpyridine metal complex was developed as a probe for selective detection of ATP and imaging of melanoma cells. The probe takes advantage of the ability of the metal complex to be transformed to its imaging competent turn-on state through assembly with ATP.

The emergence of powerful antibiotic-resistant bacteria caused by the abuse of antibiotics has become a public health problem. Photodynamic antibacterial therapy is regarded as an innovative and promising antibacterial approach due to its minor side effects and lack of drug resistance. Nevertheless, few photosensitizers (PSs) are reported to have near-infrared (NIR) emission, the ability to rapidly discriminate bacteria, and high photodynamic antibacterial efficiency. In this study, it is reported for the first time that a water-soluble NIR fluorescence emission rhodamine-based photosensitizer with aggregation-inducing emission (AIE) effects, referred to as CS-2I, can efficiently identify and kill Gram-positive bacteria. In a fluorescence imaging experiment with blended bacteria, CS-2I can selectively target Gram-positive bacteria and specifically label Gram-positive bacteria with high efficiency after only 5 min of incubation. Furthermore, CS-2I achieves complete inhibition of methicillin-resistant Staphylococcus aureus (MRSA) at an extremely low concentration (0.5 µm) and light dosage (6 J cm

Combating biofilm infections remains a challenge due to the shield and acidic conditions. Herein, an acid-responsive nanoporphyrin (PN3-NP) based on the self-assembly of a water-soluble porphyrin derivative (PN3) is constructed. Additional kinetic control sites formed by the conjugation of the spermine molecules to a porphyrin macrocycle make PN3 self-assemble into stable nanoparticles (PN3-NP) in the physiological environment. Noteworthily, near-infrared (NIR) fluorescence monitoring and synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) effects of PN3-NP can be triggered by the acidity in biofilms, accompanied by intelligent transformation into dot-like nanospheres. Thus, damage to normal tissue is effectively avoided and accurate diagnosis and treatment of biofilms is achieved successfully. The good results of fluorescence imaging-guided photo-ablation of antibiotic-resistant strains methicillin-resistant Staphylococcus aureus (MRSA) biofilms verify that PN3-NP is a promising alternative to antibiotics. Meanwhile, this strategy also opens new horizons to engineer smart nano-photosensitizer for accurate diagnosis and treatment of biofilms.

Diarylethene (DAE) photoswitch is a new and promising family of photochromic molecules and has shown superior performance as a smart trigger in stimulus-responsive materials. During the past few decades, the DAE family has achieved a leap from simple molecules to functional molecules and developed toward validity as a universal switching building block. In recent years, the introduction of DAE into an assembly system has been an attractive strategy that enables the photochromic behavior of the building blocks to be manifested at the level of the entire system, beyond the DAE unit itself. This assembly-based strategy will bring many unexpected results that promote the design and manufacture of a new generation of advanced materials. Here, recent advances in the design and fabrication of diarylethene as a trigger in materials science, chemistry, and biomedicine are reviewed.

Theranostic systems that permit both diagnosis and treatment in vivo are highly appealing means by which to meet the demands of precision medicine. However, most such systems remain subject to issues related to complex molecular design and synthesis, potential toxicity, and possible photoactivity changes. Herein, a novel supramolecular theranostic strategy involving biomarker protein activation (BPA) and a host-guest strategy is proposed. To exemplify BPA, a facile "one-for-all" nanotheranostic agent for both albumin detection and cancer treatment is demonstrated, which utilizes a nanoparticulate heavy-atom-free BODIPY dye derivative (B4 NPs). The fluorescence and photoactivity of BODIPY dyes are completely suppressed by aggregation-induced self-quenching in the nanoparticulate state. However, a Balb/c nude mouse model is used to confirm that following the disassembly of injected B4 NPs, BODIPY specifically binds albumin in vivo, accompanied by significantly enhanced biocompatibility and photothermal conversion efficiency. More importantly, this supramolecular host-guest BPA strategy enables the resultant nanoplatform to act as a facile and efficient strategy for photodynamic and photothermal immunotherapy.

Owing to their unique, nanoscale related optical properties, nanostructures assembled from molecular photosensitizers (PSs) have interesting applications in phototheranostics. However, most nanostructured PS assemblies are super-quenched, thus, preventing their use in photodynamic therapy (PDT). Although some of these materials undergo stimuli-responsive disassembly, which leads to partial recovery of PDT activity, their therapeutic potentials are unsatisfactory owing to a limited ability to promote generation reactive oxygen species (ROS), especially via type I photoreactions (i.e., not by 1 O2 generation). Herein we demonstrate that a new, nanostructured phthalocyanine assembly, NanoPcA, has the ability to promote highly efficient ROS generation via the type I mechanism. The results of antibacterial studies demonstrate that NanoPcA has potential PDT applications.

In this work, we synthesized a series of boronate ester fluorescence probes (E)‐4,4,5,5‐tetramethyl‐2‐(4‐styrylphenyl)‐1,3,2‐dioxaborolane (STBPin), (E)‐N,N‐dimethyl‐4‐(4‐(4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolan‐2‐yl)styryl)aniline (DSTBPin), (E)‐4‐(4‐(4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolan‐2‐yl)styryl)benzonitrile (CSTBPin), (E)‐2‐(4‐(4‐methoxystyryl)phenyl)‐4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolane (MSTBPin), (E)‐N,N‐dimethyl‐4‐(4‐(4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolan‐2‐yl)styryl)naphthalen‐1‐amine (NDSTBPin), and N,N‐dimethyl‐4‐(2‐(4‐(4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolan‐2‐yl)phenyl)oxazol‐5‐yl)aniline (DAPOX‐BPin) for the detection of hydrogen peroxide (H2O2). DSTBPin and MSTBPin displayed an “Off–On” fluorescence response towards H2O2, owing to the loss of the intramolecular charge transfer (ICT) excited state. Whereas, CSTBPin displayed a decrease in fluorescence intensity in the presence of H2O2 owing to the introduction of an ICT excited state. STBPin, on the other hand, produced a small fluorescence decrease, indicating the importance of an electron‐withdrawing or electron‐donating group in these systems. Unfortunately, the longer wavelength probe, NDSTBPin, displayed a decrease in fluorescence intensity. Oxazole‐based probe DAPOX‐BPin produced a “turn‐on” response. Regrettably, DAPOX‐BPin required large concentrations of H2O2 (>3 mm) to produce noticeable changes in fluorescence intensity and, therefore, no change in fluorescence was observed in the cell imaging experiments.

N-Heterocyclic carbene (NHC) boranes undergo oxidative hydrolysis to give imidazolium salts with excellent kinetic selectivity for HOCl over other reactive oxygen species (ROS), including peroxides and peroxynitrite. Selectivity for HOCl results from the electrophilic oxidation mechanism of NHC boranes, which stands in contrast to the nucleophilic oxidation mechanism of arylboronic acids with ROS. The change in polarity that accompanies the conversion of NHC boranes to imidazolium salts can control the formation of emissive excimers, forming the basis for the design of the first fluorescence probe for ROS based on the oxidation of B-H bonds. Two-photon microscope (TPM) ratiometric imaging of HOCl in living cells and tissues is demonstrated.

Azobenzene is a well-known derivative of stimulus-responsive molecular switches and has shown superior performance as a functional material in biomedical applications. The results of multiple studies have led to the development of light/hypoxia-responsive azobenzene for biomedical use. In recent years, long-wavelength-responsive azobenzene has been developed. Matching the longer wavelength absorption and hypoxia-response characteristics of the azobenzene switch unit to the bio-optical window results in a large and effective stimulus response. In addition, azobenzene has been used as a hypoxia-sensitive connector via biological cleavage under appropriate stimulus conditions. This has resulted in on/off state switching of properties such as pharmacology and fluorescence activity. Herein, recent advances in the design and fabrication of azobenzene as a trigger in biomedicine are summarized.

Colorimetric and fluorescent chemosensors have been actively studied in recent years, and this article covers our contributions to colorimetric and fluorescent chemosensors in detecting anions, metal ions, reactive oxygen species (ROS), reactive nitrogen species (RNS), biothiols, and gases. The chemosensors discussed in this article are categorized according to their corresponding analytes, and the final part is devoted to polydiacetylene-based chemosensors. We hope that this article will be beneficial in the design of chemosensors for various important analytes.

The ability to analyze highly toxic chemical warfare agents (CWAs) and related chemicals in a rapid and precise manner is essential in order to alleviate serious threats to humankind and public security caused by unexpected terrorist attacks and industrial accidents. In this investigation, we designed a o-phenylenediamine-pyronin linked dye that is capable of both fluorogenic and colorimetric discrimination between phosgene and the prototypical nerve-agent mimic, diethyl chlorophosphate (DCP) in the solution or gas phase. Moreover, this dye has been used to construct a portable kit that can be employed for real-time monitoring of DCP and phosgene in the field, both in a discriminatory manner, and in a simple and safe way.

A novel water-soluble copper(II) naphthalimide complex fluorescent probe was devised and displayed significant fluorescence turn-on response for nitric oxide and nitroxyl over other biologically relevant reactive oxygen species under physiological conditions. The dual-analyte recognition of this simple and sensitive probe was successfully applied for the imaging of exogenous and endogenous NO and HNO in living cells.

A phenolphthalein-based colorimetric probe bearing a dinitrobenzene group is reported as a thiophenol (PhSH)-selective chemodosimeter. PhSH can react with chemodosimeter 1 to afford phenolphthalein. The addition of PhSH to the aqueous solution of 1 followed by a change in pH of the resulting solution to basic induces a selective color change from colorless to pink. Furthermore, using PhSH and base as inputs and color change of 1 by naked eye as an output, leads to the construction of an AND logic gate.

A new type of bis-PDA, in which two PDAs are linked via an intervening p-phenylene group, is developed. The Bis-PDA-Ph displays exceptional thermochromic reversibility owing to the presence of unique hydrophobic interactions between alkyl chains as well as aryl moieties. The Bis-PDA-Ph has a well-packed structure that causes it to display a clear blue to red colorimetric transition at elevated temperatures. To elucidate the molecular origin of the thermochromic response, a theoretical simulation of the new PDA, the results of which successfully explain the thermochromic reversibility phenomenon, is conducted. Furthermore, Bis-PDA-Ph-embedded polymer fibers are used as a thermochromic sensor material. It displays excellent reversibility between 20–120 °C, which is the largest temperature range reported thus far for PDA based sensors. Finally, transient absorption spectroscopy is employed for the first time to analyze the temperature-dependent fluorescence change of the new PDA.

Antibiotic-resistant bacteria have emerged as a severe threat to human health. As effective antibacterial therapies, supramolecular materials display unprecedented advantages because of the flexible and tunable nature of their noncovalent interactions with biomolecules and the ability to incorporate various active agents in their platforms. Herein, supramolecular antibacterial materials are discussed using a format that focuses on their fundamental active elements and on recent advances including material selection, fabrication methods, structural characterization, and activity performance.

Polydiacetylenes (PDAs) have received increasing attention as smart materials owing to their unique properties. Upon addition of various stimuli, blue PDAs can undergo a colorimetric transition from blue to red along with a change from non-fluorescent to fluorescent. The optical changes can be readily detected by the naked eye and by using absorption and fluorescence spectrometers. These properties make PDAs excellent materials for use in platforms for sensing chemical or biological targets. In recent years, a number of biosensors and chemosensors based on the optical responses of polydiacetylenes have been reported. In this review, recent advances made in this area were discussed following a format based on different cognizing targets, including temperature, metal ions, anions, surfactants, amines, water, gas, sugars, hydrocarbons, neomycin, heparin, virus, enzymes, bacteria, and cancers. Emphasis is given to the methods used to prepare PDA sensing systems as well as their sensing performance.

A new dual-polymer electro- chromic device (ECD) composed of polyAne-(2-ene)dioxy)- thiophene) (PBueDOT) and polyani- line (PANI) with a hydrophobic molten salt electrolyte has been developed. To build this system, an alkylenedioxy ring in the BueDOT backbone was expand- ed to include a strongly electron-donat- ing alkylenedioxy bridge, and the thick- ness and surface morphology of the corresponding PBueDOT film were controlled systematically. Not only the dual-electrochromic-polymer-electrode system, but also the expanded alkyle- nedioxy ring in the BueDOT back- bone, synergistically improved the elec- trochromic performance. From the col- oration efficiency (CE) value calcula- tions, we found that the CE was en- hanced up to 930 cm 2 C � 1 . Furthermore, these ECDs showed an extremely fast response time of less than 80 ms.

A PDA based sensor, derived from a di-(2-picolyl) amine (DPA) substituted diacetylene monomer, displayed a selective colorimetric change and a large fluorescence enhancement in the presence of lead ions. The lead selective PDA-based chemosensor enabled easy detection of the presence of lead in 100% aqueous solution by the naked-eye.

Intermolecular interactions that involve aromatic rings are key pro- cesses in both chemical and biological recognition. It is common knowledge that the existence of anion-p interac- tions between anions and electron-defi- cient (p-acidic) aromatics indicates that electron-rich (p-basic) aromatics are expected to be repulsive to anions due to their electron-donating character. Here we report the first concrete theo- retical and experimental evidence of the anion-p interaction between elec- tron-rich alkylbenzene rings and a fluo- ride ion in CH3CN. The cyclophane cavity bridged with three naphthoimi- dazolium groups selectively complexes a fluoride ion by means of a combina- tion of anion-p interactions and (C H) + ···F-type ionic hydrogen bonds. 1 H NMR, 19 F NMR, and fluorescence spectra of 1 and 2 with fluoride ions are examined to show that only 2 can host a fluoride ion in the cavity be- tween two alkylbenzene rings to form a sandwich complex. In addition, the cage compounds can serve as highly se- lective and ratiometric fluorescent sen- sors for a fluoride ion. With the addi- tion of 1 equiv of F, a strongly in- creased fluorescence emission centered at 385 nm appears at the expense of the fluorescence emission of 2 centered at 474 nm. Finally, isothermal titration calorimetry (ITC) experiments were performed to obtain the binding con- stants of the compounds 1 and 2 with F as well as Gibbs free energy. The 2- F complex is more stable than the 1- F complex by 1.87 kcal mol 1 , which is attributable to the stronger anion-p in- teraction between F and triethylben- zene.

Fluorescein-functionalized silica nanoparticles (1) were prepared by sol-gel reaction, and their optical sensing abilities were studied towards finding a new type of synthetic fluorogenic chemosensor for imaging Cu 2+ ions in living cells. Interestingly, upon addition of Cu 2+ in a H 2 O suspension of 1 at pH 7.4, 1 displays large chelation-enhanced quenching (CHEQ) effects with Cu 2+ . With the exception of Cu 2+ , no significant fluorescence intensity changes were observed in the experiments with the other metal ions. These findings confirm that 1 can be useful as a fluorogenic-sensing material for the selective detection of Cu 2+ in the presence of other metal ions. This is a rare example of chromogenic sensing of a specific metal ion by functional inorganic nanomaterials. The emission change observed for chemosensor 1 in the presence of Cu 2+ is reversible by the addition of EDTA. Furthermore, the fluorescein-functionalized silica nanoparticles act as a new type of synthetic fluorogenic chemosensor for imaging Cu 2+ ions in living cells.

The synthesis of the first examples of anion receptors that utilize boron–fluoride interactions and (C–H)+···F–-type ionic hydrogen-bond interactions in the binding of F ions is reported herein. o-, m-, and p-Phenylboronic acids were linked to naphthoimidazolium through a methylene group. On the basis of fluorescence and 19F NMR studies, we have confirmed that the addition of fluoride to a boron center occurs prior to the formation of (C–H)+···F–-type ionic hydrogen bond with the imidazolium moiety. More importantly, these investigations have demonstrated that only the receptor bearing the ortho-directed boron and imidazolium exhibits enhanced fluoride binding. The increased binding ability of the asymmetric bidentate receptor of ortho-boronic acid and imidazolium towards F– enables it to sense fluoride ions in a 95:5 CH3CN/HEPES aqueous solution. The fluorescence responses to different anions were also explored; the ortho-boron-imidazolium receptor displayed ratiometric fluorescence changes and a high selectivity towards fluoride ions over other anions (Cl–, Br–, CH3CO2–, HSO4–, and H2PO4–).(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Recently, the strategy of protection–deprotection of functional groups has been widely employed to design fluorescent probes, as the protection–deprotection of functional groups often induces a marked change in electronic properties. Significant advances have been made in the development of analyte-responsive fluorescent probes based on the protection–deprotection strategy. In this tutorial review, we highlight the representative examples of small-molecule based fluorescent probes for bioimaging, which are operated via the protection–deprotection of key functional groups such as aldehyde, hydroxyl, and amino functional groups reported from 2010 to 2014. The discussion includes the general protection–deprotection methods for aldehyde, hydroxyl, or amino groups, as well as the design strategies, sensing mechanisms, and deprotection modes of the representative fluorescent imaging probes applied to bio-imaging.

Pyrophosphate anions play key roles in various biological and chemical processes. During the last few years, many exciting results have emerged regarding the development of fluorescent and colorimetric sensors for this biologically important species. In this review, we will cover the fluorescent and colorimetric chemosensors developed for the detection of pyrophosphate (PPi) since 2010.

Near-infrared (NIR) fluorescent dyes have emerged as promising modalities for monitoring the levels of various biologically relevant species in cells and organisms. The use of NIR probes enables deep photon penetration in tissue, minimizes photo-damage to biological samples, and produces low background auto-fluorescence from biomolecules present in living systems. The number of new analyte-responsive NIR fluorescent probes has increased substantially in recent years as a consequence of intense research efforts. In this tutorial review, we highlight recent advances (2010–2013) made in the development and applications of NIR fluorescent probes. The review focuses on NIR fluorescent probes that have been devised to sense various biologically important species, including ROS/RNS, metal ions, anions, enzymes and other related species, as well as intracellular pH changes. The basic principles involved in the design of functional NIR fluorescent probes and suggestions about how to expand applications of NIR imaging agents are also described.