Article-Journal

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.

The acquisition of resistance to chemotherapy is a major hurdle for successful cancer therapy. Herein, a new light-responsive drug delivery nanoparticle system is developed to overcome doxorubicin (DOX) resistance in breast cancer cells. The nanoparticles with high drug loading capacity are self-assembled from an amphiphilic polymer which is composed of a hydrophobic photosensitizer (PS) with aggregation-induced emission (AIE) characteristics and a biocompatible and hydrophilic poly(ethylene glycol) (PEG) conjugated via a reactive oxygen species (ROS) cleavable thioketal (TK) linker. The AIE PS makes the nanoparticles visible for high-quality imaging and capable of generating ROS upon light irradiation. When exposed to white light irradiation, the ROS generated from the PS could not only induce the endo-lysosomal membrane rupture, but also break the nanoparticles. This results in facilitated endo-lysosomal escape and triggered cytosol release of DOX, which can significantly improve intracellular DOX accumulation and retention in drug resistant MDA-MB-231 breast cancer cells. With light irradiation, the drug loaded nanoparticles can significantly inhibit the growth of DOX-resistant MDA-MB-231 cells. These results reveal that AIEgen based nanoparticles offer a potentially effective approach to overcome drug resistance in cancer cells.

Bioorthogonal turn-on probes have been widely utilized in visualizing various biological processes. Most of the currently available bioorthogonal turn-on probes are blue or green emissive fluorophores with azide or tetrazine as functional groups. Herein, we present an alternative strategy of designing bioorthogonal turn-on probes based on red-emissive fluorogens with aggregation-induced emission characteristics (AIEgens). The probe is water soluble and non-fluorescent due to the dissipation of energy through free molecular motion of the AIEgen, but the fluorescence is immediately turned on upon click reaction with azide-functionalized glycans on cancer cell surface. The fluorescence turn-on is ascribed to the restriction of molecular motion of AIEgen, which populates the radiative decay channel. Moreover, the AIEgen can generate reactive oxygen species (ROS) upon visible light (λ=400-700 nm) irradiation, demonstrating its dual role as an imaging and phototherapeutic agent.

The isomerization and optical properties of the cis and trans isomers of tetraphenylethene (TPE) derivatives with aggregation-induced emission (AIEgens) have been sparsely explored. We have now observed the tautomerization-induced isomerization of a hydroxy-substituted derivative, TPETH-OH, under acidic but not under basic conditions. Replacing the proton of the hydroxy group in TPETH-OH with an alkyl group leads to the formation of TPETH-MAL, for which the pure cis and trans isomers were obtained and characterized by HPLC analysis and NMR spectroscopy. Importantly, cis-TPETH-MAL emits yellow fluorescence in DMSO at −20 °C whereas trans-TPETH-MAL shows red fluorescence under the same conditions. Moreover, the geometry of cis- and trans-TPETH-MAL remains unchanged when they undergo thiol–ene reactions to form cis- and trans-TPETH-cRGD, respectively. Collectively, our findings improve our fundamental understanding of the cis/trans isomerization and photophysical properties of TPE derivatives, which will guide further AIEgen design for various applications.

The accurate detection of biological substances is highly desirable to study various biological processes and evaluate disease progression. Herein, we report a self-validated fluorescent probe which is composed of a coumarin fluorophore as the energy donor and a fluorogen with aggregation-induced emission characteristics (AIEgen) as the energy quencher linked through a caspase-3 specific peptide substrate. Unlike the traditionally widely studied fluorescence resonance energy transfer (FRET) probes, our new generation of FRET probe is non-fluorescent itself due to the energy transfer as well as the dissipation of the acceptor energy through the free molecular motion of AIEgen. Upon interaction with caspase-3, the probe displays strong green and red fluorescent signals synchronously due to the separation of the donor-quencher and aggregation of the released AIEgen. The fluorescence turn-on with dual signal amplification allows real-time and self-validated enzyme detection with a high signal-to-background ratio, providing a good opportunity to accurately monitor various biological processes in a real-time manner.