Dazhuang Xu

Facile synthesis of AIE-active amphiphilic polymers: Self-assembly and biological imaging applications.

In this work, we reported a rather facile method for fabrication of ultrabright, well dispersible and biocompatible fluorescent organic nanoparticles (FONs) with aggregation-induced emission (AIE) properties through combination of esterification and ring-opening reaction. The hydroxyl groups of Pluronic F127 was first reacted with the chloride of trimellitic anhydride chloride (TMAC), and its anhydride groups were further reacted with the amino groups of amino-terminated AIE dye (PhNH2) through ring-opening reaction. The optical properties, biocompatibility as well as cell uptake behavior of these obtained AIE-active nanoparticles (F127-TMAC-PhNH2 FONs) were examined by a series of characterization techniques and assays. We demonstrated that uniform organic nanoparticles with high water dispersibility, strong luminescence and desirable biocompatibility can be facilely obtained, which are promising for biological imaging applications. More importantly, a number of carboxyl groups were introduced into these AIE-active nanoparticles, which can be further utilized for further conjugation reaction and carrying anticancer drugs such as cisplatin. Therefore, the strategy of described in this work should be a simple and useful route for fabrication of multifunctional AIE-active luminescent nanotheranostic systems.

Towards development of a versatile and efficient strategy for fabrication of GO based polymer nanocomposites

Surface modification of graphene oxide (GO) with polymers is of particular importance for its applications. Although much progress has been made in the surface modification of GO, the surface modification of GO with synthetic polymers in aqueous solution has demonstrated to be problematic. In the present work, we report for the first time a versatile and effective method for the surface modification of GO with synthetic polymers in aqueous solution taking advantage of mussel inspired chemistry. Poly(ethylene glycol) methyl ether methacrylate and itaconic anhydride (IA) monomers were chosen to prepare hydrophilic polymers (poly(IA-co-PEGMA)) via free radical living polymerization. These hydrophilic polymers were further reacted with dopamine through ring-opening reaction between IA and dopamine, which could be highly efficiently attached to the GO surface via mussel inspired chemistry using dopamine as the adhesion component. The successful modification of GO with polymers was confirmed by using a series of characterization techniques. The resulting GO–polymer nanocomposites displayed great dispersibility in aqueous and organic solutions, making them promising for various applications. Compared with previous methods, the biomimic strategy described in this work could facilely and effectively immobilize synthetic polymers on GO in aqueous solution at room temperature and under an air atmosphere. More importantly, this strategy could also be utilized for the fabrication of almost any polymer nanocomposite because of the designability and applicability of living polymerization, and the versatility and strong adhesion of dopamine.

Fabrication and biological imaging application of AIE-active luminescent starch based nanoprobes.

Fabrication of water dispersible, biocompatible and ultrabright luminescent polymeric nanoprobes (LPNs) has been the subject of great research interest. Although a number of LPNs have been fabricated previously through different strategies, the preparation of luminescent carbohydrate polymers with aggregation-induced emission (AIE) characterstic has received only limited attention. In this work, we reported for the first time that AIE-active luminescent starch can be facilely fabricated via mixing the aldehyde-contained AIE dye 4-(1,2,2-triphenylvinyl) benzaldehyde (TPE-CHO) with carboxyl methyl starch sodium (CMS) and amino phenylboronic acid in a one-pot procedure, in which aminophenylboronic acid can serve as the linkage for conjugation of TPE-CHO and CMS. The final products (TPE-CMS LPNs) were characterized by a number of characterization techniques such as (1)H nuclear magnetic resonance spectroscopy, transmission electron microscopy, Fourier transform infrared spectroscopy and fluorescence Spectroscopy in detail. To examine their biomedical application potential, the biocompatibility as well as cell uptake behavior of TPE-CMS LPNs were further determined. We demonstrated that TPE-CMS LPNs showed high water dispersibility and strong fluorescence, well biocompatibility and efficient cell internalization behavior, making them promising candidates for various biomedical applications.

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-NH2), 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. The resultant AIE-active FPNs show high water dispersity, intensive fluorescence and low cytotoxicity. These features make these AIE-active FPNs great potential for biomedical applications. Moreover, the microwave-assisted KF reaction is simple, fast, atom economy that should be a general strategy for the fabrication of various multifunctional AIE-active FPNs. We believe this work will open up a new avenue for the preparation of AIE-active functional materials with great potential for different applications.

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. The results indicated that the obtained AIE-active amphiphilic copolymers (PEGMA-PhE) can readily self-assemble into luminescent nanoparticles (PEGMA-PhE FPNs) with high water dispersity, uniform size and morphology, red fluorescence. Cell viability examination and cell uptake behavior of PEGMA-PhE FPNs confirmed that these AIE-active FPNs possess low toxicity towards cells and can be easily internalized by cells through non-specific route. Therefore the remarkable properties of PEGMA-PhE FPNs such as high water dispersity, AIE-active fluorescence and nanoscale size as well as excellent biocompatibility make them promising for biomedical applications.

Synthesis and cell imaging applications of amphiphilic AIE-active poly(amino acid)s

The poly(amino acid)s based biomaterials have attracted great research attention over the past few decades because of their biocompatibility, biodegradability and well designability. Although much progress has achieved in the synthesis and biomedical applications of poly(amino acid)s, the synthesis of luminescent poly(amino acid)s has been rarely reported. In this work, novel amphiphilic luminescent poly(amino acid)s with aggregation-induced emission (AIE) feature have been synthesized by a new approach of controlling N-carboxy anhydride (NCA) ring-opening polymerization, in which hydrophobic 2-(4-aminophenyl)-3-(10-hexadecyl-4H-phenothiazin-3-yl)acrylonitrile (Phe-NH2) with AIE feature was used as initiator and hydrophilic oligomeric glycol functionalized glutamate (OEG-glu) NCA was acted as monomer. The successful synthesis of final Phe-OEG-Pglu polymers was confirmed by different characterization techniques. Phe-OEG-Pglu polymers possess amphiphilic properties and can self-assemble into luminescent polymeric nanoparticles (LPNs). Based on cellular imaging experiments, we demonstrated that Phe-OEG-Pglu LPNs have great potential for bio-imaging applications due to their attractive properties including strong fluorescence intensity, great water dispersibility, excellent biocompatibility and high cellular uptake efficiency.

Direct encapsulation of AIE-active dye with β cyclodextrin terminated polymers: Self-assembly and biological imaging

Aggregation-induced emission (AIE) phenomenon has attracted great attention recently and been extensively explored for biomedical applications. Nevertheless, the direct utilization of AIE-active dyes for biomedical applications has demonstrated to be enormous challenge owing to the hydrophobic nature of these AIE-active dyes. In this work, we reported the fabrication of amphiphilic AIE-active copolymers through the specific host-guest interaction between β cyclodextrin (β-CD) and an adamantine terminating tetraphenylethene derivative (TPE-Ad). In this construction system, β-CD was acted as the bridge to link TPE-Ad with PEG. The TPE-β-CD-PEG copolymers were characterized by various equipments in detail. Cytocompatibility and cell uptake behavior of TPE-β-CD-PEG were also examined to evaluate their biomedical application potential. Results demonstrated that TPE-β-CD-PEG copolymers were prone to self-assemble into luminescent nanoparticles, which exhibited high water dispersity, AIE feature and excellent biocompatibility. These features endowed TPE-β-CD-PEG great potential for biomedical applications.

Synthesis of Amphiphilic Hyperbranched AIE-active Fluorescent Organic Nanoparticles and Their Application in Biological Application.

Aggregation-induced emission (AIE) dyes have recently attracted much attention for biomedical applications for their remarkable AIE properties. However, the hydrophobic nature of AIE dyes made them difficult to be dispersed in physiological solution and problematic for biomedical application directly. Great efforts have been made to overcome this problem, and different strategies for preparation of water dispersible AIE based nanoprobes had been explored previously. However, a facile and effective strategy is still highly desirable and of great importance for the biomedical applications of AIE dye based on nanoprobes. In this work, the fabrication of amphiphilic hyperbranched fluorescent organic nanoparticles with a core-shell structure based on an AIE dye [tetraphenylethene acrylate (TPE-O-E)] and a hyperbranched polyamino compound [polyethylene imine (PEI)] through Michael addition reaction is described for the first time. The AIE dye as well as the final product PEI-TPE-O-E was characterized in detail by a number of techniques. To test their biomedical application potential, the cell viability as well as cell imaging properties of the PEI-TPE-O-E was also examined. The results showed that the PEI-TPE-O-E organic nanoparticles presented high water dispersiblity, ultrabright fluroerescence, low cytotoxicity and excellent biocompatibility, making them promising for biological imaging and gene delivery applications.

A powerful “one-pot” tool for fabrication of AIE-active luminescent organic nanoparticles through the combination of RAFT polymerization and multicomponent reactions

Multicomponent reactions (MCRs) have recently received increasing attention for the synthesis of structural complexity in a single step from three or more reactants. They have also been considered as a powerful tool for the construction of sequence-controlled multifunctional polymers owing to their good substrate adaptability, simple operation and high efficiency. In this work, we reported methods that are a combination of the three-component mercaptoacetic acid locking imine (MALI) reaction and reversible addition fragmentation chain transfer (RAFT) polymerization in one pot to form luminescent organic nanoparticles (LONs) with aggregation-induced emission (AIE) features, high-brightness, great water dispersibility, ultra-small nanoscale size and excellent biocompatibility. In the reaction system, the MALI reaction and RAFT polymerization happened simultaneously in a “one-pot” route. On the one hand, the AIE-active organic dye with one amino group ((Z)-3-(4-aminophenyl)-2-(10-hexadecyl-10H-phenothiazin-3-yl)acrylonitrile) (named as Phe-NH2) was conjugated with an aldehyde-containing monomer (10-undecenal) by the MALI reaction, while the aldehyde-containing monomer was copolymerized with the hydrophilic monomer polyethylene glycol methyl methacrylate (PEGMA) through RAFT polymerization at the same time. Compared with other fabrication strategies, “one-pot” strategies possess some advantages such as high efficiency, simplicity, and atom economy. On the other hand, due to the good applicability of RAFT polymerization and the MALI reaction, many other multifunctional AIE-active LONs could also be fabricated via adjusting the function of the substrates. Therefore, this strategy should be a general and important route for fabrication of AIE-active materials for different applications.

Fabrication of amphiphilic fluorescent nanoparticles with an AIE feature via a one-pot clickable mercaptoacetic acid locking imine reaction: synthesis, self-assembly and bioimaging

Fluorescent organic nanoparticles (FNPs) with intensive luminescence are widely applied in various biomedical fields, but the malicious aggregation caused quenching effect of conventional organic dyes hampers their biomedical application. In this work, we report a facile and highly efficient method for fabrication of FNPs with a stable cross-linked structure and enhanced luminescence via a one-pot mercaptoacetic acid locking imine reaction, in which a hydrophobic aggregation induced emission (AIE) dye (AHAn) and hydrophilic polylysine (Plys) were used as two reaction components, while mercaptoacetic acid acted as the lock to conjugate AHAn and Plys. The final amphiphilic fluorescent materials (Plys&AHAn&Plys) are readily formed FNPs in aqueous solution and exhibit high water dispersibility and strong luminescence. Furthermore, Plys&AHAn&Plys FNPs display low toxicity and good biological imaging performance. Altogether, we have developed a rather facile one-pot multicomponent reaction (MCR) to fabricate AIE active FNPs, which shows many promising properties for biomedical applications. More importantly, the MCR strategy could also be used for fabrication of many other multifunctional AIE active polymeric nanoprobes due to its good substrate adaptability and high efficiency.