Structure-based drug discovery of novel penta- or hexa-bicyclo-pyrazolone derivatives as potent and selective AXL inhibitors.

AXL is a promising antitumor target due to its important role in tumor growth, poor survival, metastasis, immunosuppression, and drug resistance. Herein, we employed molecular modeling-assisted structural optimization strategies to design and synthesize a series of penta- or hexa-bicyclo-pyrazolone derivatives as novel AXL inhibitors. Compounds with high enzymatic and cellular potencies against AXL are described.

Development of Cysteic Acid-Modified FAP Radioligands for Enhanced Renal Clearance: From Preclinical Optimization to First-in-Human Study.

Fibroblast activation protein (FAP)-targeting radioligands hold promise for cancer theranostics. Cyclic peptide-based DOTA-FAP-2286 radioligands have demonstrated high kidney uptake and retention, raising concerns regarding potential nephrotoxicity. Hence, we aimed to design three cysteic acid-modified FAP-targeting cyclic peptide ligands (DOTA-C1/C2/C3-FAP-2286) for reducing renal retention and optimizing pharmacokinetic properties.

Construction of cellulose-based hybrid hydrogel beads containing carbon dots and their high performance in the adsorption and detection of mercury ions in water.

Cellulose-based adsorbents have been extensively developed in heavy metal capture and wastewater treatment. However, most of the reported powder adsorbents suffer from the difficulties in recycling due to their small sizes and limitations in detecting the targets for the lack of sensitive sensor moieties in the structure. Accordingly, carbon dots (CDs) were proposed to be encapsulated in cellulosic hydrogel beads to realize the simultaneous detection and adsorption of Hg (II) in water due to their excellent fluorescence sensing performance.

PEGylated AIEgens for dual sensing of ATP and HS and cancer cells photodynamic therapy.

Fluorescent sensors have been widely applied for biosensing, but probes for both multiple analytes sensing and photodynamic therapy (PDT) effect are less reported. In this article, we reported three AIE-based probes anchored with different mass-weight polyethylene glycol (PEG) tails, i.e.

A novel polymer-based probe for fluorescently ratiometric sensing of hydrogen sulfide with multiple applications.

Hydrogen sulfide (HS) as an endogenous signaling molecule, plays an irreplaceable role in many important physiological activities. It is also closely related to sewage treatment, wine quality evaluation, and food spoilage. Herein, we have successfully synthesized a novel polymer-based probe P1 for fluorescently ratiometric sensing of HS with a high selectivity and sensitivity.

Bis-Schiff base cellulosic nanocrystals for Hg (II) removal from aqueous solution with high adsorptive capacity and sensitive fluorescent response.

Mercury pollution in aqueous solutions is a severe problem in environmental protection and the contaminated water may cause serious risks to human health. Based on the constant development of adsorptive materials, adsorption technique is widely applied as an efficient and convenient approach to eliminate mercury species from waters. In this work, we report a one-pot procedure to prepare a bis-Schiff base cellulosic adsorbent to integrate the advantages of large adsorptive capacity and excellent fluorescent recognition towards mercury ions.

Dansyl-labelled cellulose as dual-functional adsorbents for elimination and detection of mercury in aqueous solution via aggregation-induced emission.

Dansyl chloride fluorophore exhibits typical aggregation induced fluorescence emission behavior in acetone/water solution. To realize the integration of detective and adsorptive functions, dansyl chloride is covalently immobilized on cellulose substrate to fabricate an efficient adsorbent for mercury ions in water. The as-prepared material exhibits excellent fluorescence sensing performance exclusively for Hg (II) with the presence of other metal ions.

A GSH-activated AIE-based polymer photosensitizer for killing cancer cells.

Developing efficient photosensitizers which are sensitive to therapeutic tumor signals, but non-toxic to normal cells has always been a tremendous challenge in photodynamic therapy (PDT) process. Herein, a novel copolymer P1 was developed by ring-opening metathesis polymerization (ROMP) with disulfide bond linked ferrocene-norbornene dyad NB-SS-PyFc and the aggregation-induced emission (AIE) fluorephore anchored norbornene NB-TPE, and its nanoparticles (NPs) were obtained by using the amphiphilic Pluronic F-127 as the surfactant via a nanoprecipitation method. The P1 NPs show a weak emission and a low O generation for the quenching effect from the ferrocene moiety to the AIE group.

Aminoquinoline-anchored polynorbornene for sequential fluorescent sensing of Zn and ATP.

A novel aminoquinoline functionalized norbornene (1) and its ring-opening metathesis polymerization (ROMP) copolymer P1 have been designed and synthesized. The polymer probe P1 can self-assemble nano aggregation in aqueous solution. The fluorescent experiments revealed that both 1 and P1 show a ratiometric fluorescence response toward Zn over other mental ions in Tris-HCl buffer solution, with the polymer probe P1 shows a better photostability and higher binding affinity than that of the small molecular probe 1.

Direct grafting of cellulose nanocrystals with poly(ionic liquids) via Gamma-ray irradiation and their utilization for adsorptive removal of CR.

In this work, a simple but effective method based on Gamma-ray initiated polymerization was reported for the first time through direct irradiation of CNCs and ionic liquid monomer to obtain poly (ionic liquids) functionalized CNCs (IL@CNCs). The adsorptive removal of Congo red (CR) from aqueous solution by IL@CNCs was also examined and the influence of contact time, pH values, initial concentrations and temperature on adsorption behavior was investigated in detail. Under the same adsorption conditions, the adsorption capacity was increased from 59.

Pyridinium-conjugated polynorbornenes for nanomolar ATP sensing using an indicator displacement assay and a PET strategy.

An indicator displacement assay, namely polymeric PNPY-n/UD consisting of a cationic polynorbornene backbone with pyridinium functional groups (PNPY-1,2,3) and an anionic uranine dye (UD) as an indicator, has been developed for highly sensitive "turn-on" fluorescence sensing of ATP. While PNPY-1/UD itself is non-emissive, a bright green fluorescence signal was observed in the presence of ATP [ = 2.17 × 10 M, LOD = 5.

AIE based GSH activatable photosensitizer for imaging-guided photodynamic therapy.

A novel ferrocene decorated vinyl pyridinium-substituted tetraphenylethylene (TPEPY-S-Fc) linked by a disulfide bond was designed as a GSH activatable photosensitizer by aggregation-induced emission for imaging-guided photodynamic therapy of cancer cells.

Nanomolar detection of adenosine triphosphate (ATP) using a nanostructured fluorescent chemosensing ensemble.

We report a novel nanostructured chemosensing ensemble PyNp-C13/UD, obtained by self-assembling uranine dye (UD) and an amphiphilic pyridinium salt PyNp-C13. The ensemble was developed for the fluorescence turn-on sensing of ATP in aqueous solutions and inside living cells. The assembly operates via an indicator displacement assay (IDA) method with an ultra-low detection limit of 6.

Fluorescence-sensitive adsorbent based on cellulose using for mercury detection and removal from aqueous solution with selective "on-off" response.

A new fluorogenic bio-adsorbent was successfully synthesized for detection and adsorption of mercury ions in aqueous solution. It showed high sensitivity in removing Hg (II) at low concentration with a detection limit of 84 ppb which was below the maximum discharge standard in enterprise drain off water in China, besides, the adsorbent had good selectivity towards Hg (II) among numerous kinds of cations in water that it showed fluorescent quenching properties for Hg (II) ions due to photo-induced electron transfer. In addition, batch adsorption experiments were investigated to study the influence of initial concentration of metal ions, contact time, pH of the solution on the adsorption capacity.

Multifunctional Fluorescent Nanoprobe for Sequential Detections of Hg Ions and Biothiols in Live Cells.

Herein, we report an amphiphilic fluorescent probe consisting of a dansyl fluorophore as a reporter and a hydrophobic cetyl chain bridged by a triazole unit. The cetyl-based probe can self-assemble to form nanoaggregates in aqueous solution, as confirmed by Tyndall effect, dynamic light scattering (DLS), and transmission electron microscopy (TEM) measurements. This probe exhibited an "on-off" fluorescence quenching response toward Hg ions in aqueous solution over other tested metal ions.

AIE-active self-assemblies from a catalyst-free thiol-yne click reaction and their utilization for biological imaging.

Aggregation-induced emission (AIE) should be the most interest fluorescent phenomenon over the past few decades. The luminescence polymeric nanoparticles (LPNs) with AIE characteristic have attracted great research attention for biological imaging and many other biomedical applications owing to their good biocompatibility and negative toxicity. However, the preparation of LPNs with desirable optical properties using traditional organic dyes still remains a great challenge for the aggregation-caused quenching (ACQ) effect and aggregation of hydrophobic dyes in the core of LPNs.

Facile fabrication of organic dyed polymer nanoparticles with aggregation-induced emission using an ultrasound-assisted multicomponent reaction and their biological imaging.

Ultrasound as a powerful technique has increasingly been used in both industry and academia in recent years. Herein, an efficient approach to the ultrafast preparation of cross-linked fluorescent copolymers (PEGMA-AEMA-TPE) with aggregation-induced emission (AIE) via an ultrasound-assisted multicomponent reaction (MCR) is described. A number of characterization techniques were carried out to certify the successful preparation of these AIE-active copolymers.

Ultrafast microwave-assisted multicomponent tandem polymerization for rapid fabrication of AIE-active fluorescent polymeric nanoparticles and their potential utilization for biological imaging.

The fabrication and biomedical applications of fluorescent polymeric nanoparticles (FPNs) with aggregation-induced emission (AIE) feature has attracted the most intensive research interest since the first discovery of AIE phenomenon by Tang' group. Although great attention has been devoted to preparation of AIE-active FPNs, an efficient, facile and versatile strategy is still highly desirable to advance their biomedical applications. In this work, a one-pot microwave-assisted multicomponent tandem polymerization was proposed to fabricate AIE-active FPNs based on a microwave-assisted Kabachnik-Fields (KF) reaction, which involves the conjugation of aldehyde group containing polyethylene glycol (CHO-PEG-CHO) and amino-group terminating AIE dye (HN-PhE-NH) using diethyl phosphate as the lock.

Synthesis of fluorescent dendrimers with aggregation-induced emission features through a one-pot multi-component reaction and their utilization for biological imaging.

Hyperbranched polymers have attracted wide research attention owing to their unique topological structure, physicochemical properties and great potential for applications such asadditives, drug delivery, catalysts and nanotechnology. Among these, the polyamidoamine(PAMAM) dendrimers are some of the most important dendrimers. However, the synthesis and biomedical applications of fluorescent PAMAM dendrimers have received only limited attention.

A facile one-pot Mannich reaction for the construction of fluorescent polymeric nanoparticles with aggregation-induced emission feature and their biological imaging.

Multicomponent reactions (MCRs) have recently attracted great attention as one of the most important tools for the construction of various organic compounds in modern organic chemistry. In this work, we introduced an efficient one-pot strategy to successfully fabricate the fluorescent polymeric nanoparticles (FPNs) with aggregation-induced emission (AIE) characteristic via the conjugation of hyperbranched polyamino compound polyethyleneimine (PEI), AIE dye (named as PhE-OH) and paraformaldehyde (PF) through a Mannich reaction. The final amphiphilies (PEI-PF-PhE) can self-assemble into micelles in aqueous solution.

Facile fabrication of luminescent polymeric nanoparticles containing dynamic linkages via a one-pot multicomponent reaction: Synthesis, aggregation-induced emission and biological imaging.

Luminescent polymeric nanoparticles (LPNs) with aggregation-induced emission (AIE) feature have emerged as the most promising candidates for biological imaging owing to their unique AIE feature, great water dispersity, strong fluorescence, low cytotoxicity and biocompatibility. Although numerous successful strategies for construction of AIE-active LPNs have been developed, the preparation of dynamic linkages containing AIE-active LPNs based on multicomponent reactions has been rarely reported. In this work, we report a facile method for the formation of AIE-active LPNs via a one-pot conjugation of PEG-B(OH), 1-thioglycerol and AIE-active dye PhE-alc in short time under rather mild reaction conditions (e.

Microwave-assisted multicomponent reactions for rapid synthesis of AIE-active fluorescent polymeric nanoparticles by post-polymerization method.

The development of simple and effective methods for synthesis of fluorescent polymeric nanoparticles (FPNs) with aggregation-induced emission (AIE) plays an important role for the biomedical applications of AIE-active FPNs. In present work, we developed a facile strategy for the fabrication of AIE-active FPNs by a post-polymerization method based on the microwave-assisted Kabachnik-Fields (KF) reaction, which can conjugate with poly(PEGMA-NH), AIE-active dye (TPE-CHO) and diethyl phosphate (DP) under microwave irradiation within 5min. The characterization results confirm that PEGMA-TPE FPNs are successfully prepared through the microwave-assisted KF reaction.

Preparation of AIE-active fluorescent polymeric nanoparticles through a catalyst-free thiol-yne click reaction for bioimaging applications.

Fluorescent polymeric nanoparticles (FPNs) with aggregation-induced emission (AIE) characteristics have attracted much attention for biomedical applications due to their remarkable AIE feature, high water dispersity and desirable biocompatibility. The development of facile and effective strategies for fabrication of these AIE-active FPNs therefore should be of great importance for their biomedical applications. In this work, we reported that a catalyst-free thiol-yne click reaction can be utilized for fabrication of AIE-active FPNs in short reaction time and even without protection of inert gas.

A self-assembled amphiphilic imidazolium-based ATP probe.

A novel amphiphilic imidazolium-based probe containing a dansyl fluorophore and a long cetyl chain has been developed for ATP recognition. The probe forms self-assembled micelle-like aggregates at low concentration in its aqueous solution and can selectively recognize ATP among other bioactive anions with a significant enhancement in fluorescence emission.

Amide-Triazolium-Appended Anthracenes for Turn-On Fluorescence Sensing of Anions in Noncompetitive and Competitive Solvents.

A new anthracene-based receptor bearing two arms of amide-triazolium anion-binding sites, and its counterpart compound with one amide-triazolium arm, have been synthesized and characterized. Their ability to bind anions in different solvents (CH CN, CHCl and DMSO) has been investigated in detail by using fluorescence techniques. Both compounds exhibited significant fluorescence turn-on sensing of F and H PO ions in noncompetitive and competitive environments with different binding modes.