Article-Journal

A signal amplified fluorogenic ELISA based on self-clickable fluorogens with aggregation-induced emission characteristics (AIEgen) as a substrate was developed for ultrasensitive immunoassay.

The development of red fluorophores with efficient solid-state emission is still challenging. Herein, a red fluorophore 1 with aggregation-induced emission (AIE) and excited-state intramolecular proton transfer (ESIPT) characteristics is rationally designed and facilely synthesized by attaching an electron-donor diethylamine and an electron-acceptor maleonitrile group to salicyladazine. In contrast to many red fluorophores which undergo serious aggregation-caused quenching (ACQ), compound 1 emits bright red fluorescence (λem = 650 nm, ΦF = 24.3%) in the solid state with a large Stokes shift of 174 nm. Interestingly, control compounds 2 and 3, which have similar structures as 1, exhibit obvious aggregation-caused quenching (ACQ) characteristics. The difference in the crystal structures of 1, 2, and 3 reveals that the interplanar spacing among molecules plays a decisive role in realizing the AIE characteristics of 1. Moreover, when the hydroxyl group of 1 was substituted by an esterase reactive acetoxyl, a fluorescence light-up probe 4 was developed for sensing of esterase based on the selective reaction between 4 and esterase to generate the AIE and ESIPT active molecule 1. The linear range for in vitro quantification of esterase is 0.01–0.15 U/mL with a detection limit of 0.005 U/mL. Probe 4 was also successfully applied to image esterase in mitochondria of living cells.

Photodynamic therapy (PDT), which relies on photosensitizers (PS) and light to generate reactive oxygen species to kill cancer cells or bacteria, has attracted much attention in recent years. PSs with both bright emission and efficient singlet oxygen generation have also been used for image-guided PDT. However, simultaneously achieving effective 1 O2 generation, long wavelength absorption, and stable near-infrared (NIR) emission with low dark toxicity in a single PS remains challenging. In addition, it is well known that when traditional PSs are made into nanoparticles, they encounter quenched fluorescence and reduced 1 O2 production. In this contribution, these challenging issues have been successfully addressed through designing the first photostable photosensitizer with aggregation-induced NIR emission and very effective 1 O2 generation in aggregate state. The yielded nanoparticles show very effective 1 O2 generation, bright NIR fluorescence centered at 820 nm, excellent photostability, good biocompatibility, and negligible dark in vivo toxicity. Both in vitro and in vivo experiments prove that the nanoparticles are excellent candidates for image-guided photodynamic anticancer therapy.

Long-term tracking of bone marrow stromal cells in a rat photothrombotic ischemia model is achieved by organic nanoparticles with aggregation-induced emission. On page 6576, L.-D. Liao, B. Liu, and co-workers demonstrate the design and synthesis of the nanoparticles to realize low phototoxicity and high stability. These nanoparticles show promising potential for monitoring the transplanted stem cells in cell therapy.

By introducing nonlinear optical (NLO) chromophores to calix[4]resorcinarene, a non-centrosymmetric core, through powerful click chemistry reactions, two branched macromolecules (CRA-CzAZO and CRA-CzCSN) were obtained in satisfactory yields for photorefractive (PR) applications. In comparison with traditional PR materials, which usually need a high external electric field or a poling procedure to realize the PR effect, CRA-CzAZO and CRA-CzCSN can show a good all-optical PR (AOPR) effect, namely showing the PR effect without an external electric field, due to their special non-centrosymmetric topological structure. Two-beam coupling technology is used to prove the PR performance, and a high coupling gain coefficient of 83.2 cm?1 is realized with zero field through optically transparent films of CRA-CzAZO doped with 30% N-ethyl-carbazole as the plasticizer and photoconductor, and 1% C60 as the photosensitizer, indicating that a CRA-CzAZO based composite thin film could serve as a good candidate for real PR applications. More importantly, CRA-CzAZO and CRA-CzCSN provide a new simple design strategy for AOPR materials.

Stem-cell based therapy is an emerging therapeutic approach for ischemic stroke treatment. Bone marrow stromal cells (BMSCs) are in common use as a cell source for stem cell therapy and show promising therapeutic outcomes for stroke treatment. One challenge is to develop a reliable tracking strategy to monitor the fate of BMSCs and assess their therapeutic effects in order to improve the success rate of such treatment. Herein, TPEEP, a fluorogen with aggregation-induced emission characteristics and near-infrared emission are designed and synthesized and further fabricated into organic nanoparticles (NPs). The obtained NPs show high fluorescence quantum yield, low cytotoxicity with good physical and photostability, which display excellent tracking performance of BMSCs in vitro and in vivo. Using a rat photothrombotic ischemia model as an example, the NP-labeled BMSCs are able to migrate to the stroke lesion site to yield bright red fluorescence. Immunofluorescence staining shows that the NP labeling does not affect the normal function of BMSCs, proving their good biocompatibility in vivo. These merits make TPEEP NP a potential cell tracker to evaluate the fate of BMSCs in cell therapy.

We report a facile encapsulation approach to realize bright far red/near-infrared (FR/NIR) fluorescence and efficient singlet oxygen ((1)O2) production of organic fluorogens with aggregation-induced emission (AIEgen) and intramolecular charge transfer (ICT) characteristics for image-guided photodynamic cancer cell ablation. The synthesized AIEgen BTPEAQ possesses donor-acceptor-donor structure, which shows bright fluorescence in solid state. Due to the strong ICT effect, BTPEAQ exhibits poor emission with almost no (1)O2 generation in aqueous solution. Encapsulation of BTPEAQ by DSPE-PEG block copolymer yields polymer-shelled dots, which show enhanced brightness with a fluorescence quantum yield of 3.9% and a (1)O2 quantum yield of 38%. Upon encapsulation by silica, the formed SiO2-shelled dots show much improved fluorescence quantum yield of 12.1% but with no obvious (1)O2 generation. This study clearly demonstrates the importance of encapsulation approach for organic fluorophores, which affects not only the brightness but also the (1)O2 production. After conjugating the polymer-shelled AIE dots with cRGD peptide, the obtained BTPEAQ-cRGD dots show excellent photoablation toward MDA-MB-231 cells with integrin overexpression while keeping control cells intact.

Conjugated polymers have been increasingly studied for photothermal therapy (PTT) because of their merits including large absorption coefficient, facile tuning of exciton energy dissipation through nonradiative decay, and good therapeutic efficacy. The high photothermal conversion efficiency (PCE) is the key to realize efficient PTT. Herein, a donor-acceptor (D-A) structured porphyrin-containing conjugated polymer (PorCP) is reported for efficient PTT in vitro and in vivo. The D-A structure introduces intramolecular charge transfer along the backbone, resulting in redshifted Q band, broadened absorption, and increased extinction coefficient as compared to the state-of-art porphyrin-based photothermal reagent. Through nanoencapsulation, the dense packing of a large number of PorCP molecules in a single nanoparticle (NP) leads to favorable nonradiative decay, good photostability, and high extinction coefficient of 4.23 �� 104 m-1 cm-1 at 800 nm based on porphyrin molar concentration and the highest PCE of 63.8% among conjugated polymer NPs. With the aid of coloaded fluorescent conjugated polymer, the cellular uptake and distribution of the PorCP in vitro can be clearly visualized, which also shows effective photothermal tumor ablation in vitro and in vivo. This research indicates a new design route of conjugated polymer-based photothermal therapeutic materials for potential personalized theranostic nanomedicine.

Far-red (FR)/near-infrared (NIR) photosensitizer is highly desirable in image-guided photodynamic cancer therapy. Herein, a new conjugated polymer of poly(1,2-bis(4-((6-bromohexyl)oxy)phenyl)-1,2-diphenylethene-co-alt-9,10-anthraquinone) (PTPEAQ) consisting of tetraphenylethylene (TPE), an iconic aggregation-induced emission (AIE) active group as the electron donor, and anthraquinone (AQ) as the acceptor, is prepared for the first time through one-pot Suzuki polymerization. Encapsulation of PTPEAQ with a block copolymer followed by surface functionalization with anti-Her2 affibody yields PTPEAQ-NP-HER2. It shows bright AIE-active FR/NIR emission and efficient singlet oxygen generation under visible light irradiation, which has been successfully used for photodynamic cancer cell ablation using SKBR-3 cells, a type of breast cancer cell with HER2 overexpression on cell membrane, as an example.

Porphyrins have long been used as fluorescence imaging contrast agents. However, they often suffer from aggregation-caused quenching (ACQ) which limits their maximal imaging ability. It is desirable to design new porphyrin derivatives exhibiting aggregation induced emission enhancement (AIEE) with a high photoluminescence (PL) intensity in an aggregated state. Herein, we transform porphyrin from an ACQ molecule to an AIEE one by simply decorating a porphyrin core with four tetraphenylethene arms. We further encapsulate the new AIE porphyrin into nanoparticles and examine their fluorescence imaging in vitro with HeLa cells. This research demonstrates a general approach to produce AIEE porphyrin derivatives that could potentially enhance their performance in various areas.