Reaction-based AIE-active Fluorescent Probes for Selective Detection and Imaging

Fluorescent probes have been widely investigated for their features of rapid response, easy operation and high sensitivity. Among them, reaction-based fluorescent probes, for their unique reaction-based nature, guarantee them with excellent selectivity, effectively avoiding the possible interference from other chemical and biological species in physiological environment. Conventional reaction-based fluorescent probes are aggregation-caused quenching (ACQ) fluorophores. The application of these kinds of probes are limited for their poor photostability and narrow Stokes shifts. Compared with ACQ fluorophores, aggregation-induced emission (AIE) fluorophores become emissive in aggregation states with higher signal-to-noise ratio, better photostability and larger Stokes shifts. In this review, we summarize the latest developed reaction-based AIE-active probes, including the design principle and application in various sensing systems and give an outlook for the future development of this kind of promising fluorescent probes.     

Silver@quercetin Nanoparticles with Aggregation-Induced Emission for Bioimaging In Vitro and In Vivo

Fluorescent materials based on aggregation-induced emission luminogens (AIEgens) have unique advantages for in situ and real-time monitoring of biomolecules and biological processes because of their high luminescence intensity and resistance to photobleaching. Unfortunately, many AIEgens require time-consuming and expensive syntheses, and the presence of residual toxic reagents reduces their biocompatibility. Herein, silver@quercetin nanoparticles (Ag@QCNPs), which have a clear core–shell structure, were prepared by redox reaction of quercetin (QC), a polyphenolic compound widely obtained from plants, including those used as foods, and silver ions. Ag@QCNPs show both aggregation-induced luminescence and the distinct plasma scattering of silver nanoparticles, as well as good resistance to photobleaching and biocompatibility. The Ag@QCNPs were successfully used for cytoplasmic labeling of living cells and for computerized tomography imaging in tumor-bearing mice, demonstrating their potential for clinical applications.     

AIE-Featured Redox-Sensitive Micelles for Bioimaging and Efficient Anticancer Drug Delivery

In the present study, an amphiphilic polymer was prepared by conjugating methoxy poly(ethylene glycol) (mPEG) with tetraphenylethene (TPE) via disulfide bonds (Bi(mPEG-S-S)-TPE). The polymer could self-assemble into micelles and solubilize hydrophobic anticancer drugs such as paclitaxel (PTX) in the core. Combining the effect of TPE, mPEG, and disulfide bonds, the Bi(mPEG-S-S)-TPE micelles exhibited excellent AIE feature, reduced protein adsorption, and redox-sensitive drug release behavior. An in vitro intracellular uptake study demonstrated the great imaging ability and efficient internalization of Bi(mPEG-S-S)-TPE micelles. The excellent anticancer effect and low systemic toxicity were further evidenced by the in vivo anticancer experiment. The Bi(mPEG-S-S)-TPE micelles were promising drug carriers for chemotherapy and bioimaging.     

Functionalized Fluorescent Organic Nanoparticles Based AIE Enabling Effectively Targeting Cancer Cell Imaging

We report a fluorescent dye TM by incorporating the tetraphenylethylene (TPE) and cholesterol components into perylene bisimides (PBI) derivative. Fluorescence emission spectrum shows that the dye has stable red emission and aggregation-induced emission (AIE) characteristics. The incorporation of cholesterol components triggers TM to show induced chirality through supramolecular self-assembly. The cRGD-functionalized nanoparticles were prepared by encapsulating fluorescent dyes with amphiphilic polymer matrix. The functionalized fluorescent organic nanoparticles exhibit excellent biocompatibility, large Stokes’ shift and good photostability, which make them effective fluorescent probes for targeting cancer cells with high fluorescence contrast.     

A Branched Tripeptide with an Anion-Binding Motif as a New Delivery Carrier for Efficient Gene Transfection

Branched and dendrimeric cationic peptides have shown better transfection efficiency than linear peptides, owing to their superior capacity for inducing DNA condensation. We have designed and synthesized two analogously guanidinocarbonylpyrrole-substituted (GCP-substituted) branched cationic tripeptides that provide extremely strong electrostatic attraction towards DNA. Both ligands 1 and 2 can bind to DNA and form condensed complexes, owing to the branched structure and high positive charges, as demonstrated by isothermal titration calorimetry (ITC), ζ potential and atomic force microscopy (AFM). After the replacement of the carboxylate group by an amide group, binding of ligand 2 to DNA shows exothermic enthalpy and positive entropy changes relative to ligand 1 . Rational interpretation would suggest that ligand 2 might aid the translocation of plasmid pF143 to HEK 293T cells, showing high gene transfection efficiency. This work therefore provides a facile way, by modifying a branched cationic tripeptide with GCP, to turn a peptide even a tripeptide into an efficient gene transfection vector.     

阳离子脂质体基因转染研究

目的：评价阳离子脂质体介导基因转染宫颈癌细胞的转染效果,优化对宫颈癌细胞的转染条件。方法：以荧光素酶基因pGL3为报告基因,分析影响阳离子脂质体Lipofectamine 2000转染Hela效率的因素。结果：通过细胞转染实验,得出脂质体与pDNA的稀释液混合较佳等待时间为30 min,脂质体/pDNA复合物与细胞接触的转染时间为4 h,转染效率较高。结论：Lipofectamine2000 Hela细胞转染效率较高。     

Microsegregation: From Basic Concepts to Complexity in Liquid Crystal Self-Assembly

This review is focused on the basic concepts of microsegregation and a fundamental understanding of the formation of positionally ordered LC phases based on micro- and nanophases, interaction parameters and interfaces. Selected examples were chosen from the actual literature to illustrate the concepts. Microsegregation is the basis of classical LC phases and cybotaxis, and most importantly, it paves the way to a huge number of new LC phases. Beside the distinct modes of micellar packing motifs and liquid quasicrystals formed by self-assembly of dendritic molecules, attention is also focused on the specific effects of rigid anisometric units and polyphilicity. Honeycomb LC phases, vesicular LC phases and mesophases with 3D-lattices lead to enhanced complexity of LC self-assembly.     

脂质体协同磷酸钙/DNA共沉淀的基因转染研究

利用商业化的脂质体Lipofectamine 2000协同高Ca/P值的Ca-P/DNA共沉淀提高基因转染效率,并保持了其较低的细胞毒性。结果表明,当Ca/P值为150时,加入0.2μL脂质体Lipofectamine 2000可得到高基因转染效率和低细胞毒性。这种脂质体协同Ca-P/DNA共沉淀技术有望在基因治疗中得到广泛应用。     

Silver-Nanoparticle-Embedded Short Amphiphilic Peptide Nanostructures and Their Plausible Application to Reduce Bacterial Infections

The microbiota-gut-brain axis (GBA) plays a critical role in the development of neurodegenerative diseases. Dysbiosis of the intestinal microbiome causes a significant alteration in the gut microbiota of Alzheimer's disease (AD) patients, followed by neuroinflammatory processes. Thus, AD beginning in the gut is closely related to an imbalance in gut microbiota, and hence a multidomain approach to reduce this imbalance by exerting positive effects on the gut microbiota is needed. In one example, a tyrosine-based short peptide amphiphile (sPA) was used to synthesize antibacterial AgNPs−sPA nanostructures. Such nanostructures showed high biocompatibility and low cytotoxicity, and therefore work as model drug delivery agents for addressing local bacterial infections. These may have therapeutic value for the treatment of microbiota-triggered progression of neurodegenerative diseases.     

镓酸碱土体系的发光性能研究

采用高温固相合成法研究了镓酸碱土体系的相关系及此体系的荧光性能。研究了以MGa2O4（M=Ba,Sr,Ca）为荧光粉的基质合成条件;探讨了MGa2O4（M=Ba,Sr,Ca）掺杂Eu3＋、Tb3＋等为激活剂的荧光粉的光致发光性能。     

Adaptive Synthesis of Functional Amphiphilic Dendrons as a Novel Approach to Artificial Supramolecular Objects

Supramolecular structures, such as micelles, liposomes, polymerosomes or dendrimerosomes, are widely studied and used as drug delivery systems. The behavior of amphiphilic building blocks strongly depends on their spatial distribution and shape of polar and nonpolar component. This report is focused on the development of new versatile synthetic protocols for amphiphilic carbosilane dendrons (amp-CS-DDNs) capable of self-assembly to regular micelles and other supramolecular objects. The presented strategy enables the fine modification of amphiphilic structure in several ways and also enables the facile connection of a desired functionality. DLS experiments demonstrated correlations between structural parameters of amp-CS-DDNs and the size of formed nanoparticles. For detailed information about the organization and spatial distribution of amp-CS-DDNs assemblies, computer simulation models were studied by using molecular dynamics in explicit water.     

聚集诱导发光分子TPE-2SO3Na+与九种蛋白相互作用初探

四苯基乙烯(TPE)衍生物TPE-2SO3Na+是一种水溶性的聚集诱导发光分子。研究了pH值对TPE-2SO3Na+荧光强度的影响、TPE-2SO3Na+对不同蛋白的荧光响应、MP/PNP对TPE-2SO3Na+荧光的猝灭效应以及MP存在下TPE-2SO3Na+对不同类型蛋白的荧光响应。结果表明,TPE-2SO3Na+的荧光强度随着pH值的增大而减弱;在pH值8.0下,TPE-2SO3Na+对不同类型蛋白的荧光响应不同,MPH、BSA、Pap使TPE-2SO3Na+荧光强度增强,增强顺序为:BSA>MPH>Pap,且蛋白浓度越大,TPE-2SO3Na+荧光增强效果越明显;MP和PNP都会对TPE-2SO3Na+产生荧光猝灭,并且PNP的猝灭效率是MP的6倍。用MP猝灭TPE-2SO3Na+检测蛋白后发现BSA、Pap、Hb有荧光响应,通过加入MP能够使TPE-2SO3Na+特异性识别BSA,为今后进一步的荧光探针筛选鉴别蛋白方法的建立奠定了基础。     

Theranostic Nanoprobes with Aggregation-Induced NIR-II Emission: from Molecular Design to Biomedical Application

The development of fluorophores with other powerful features has received much attention for the diagnosis and treatment of diseases. Nanoprobes (NPs) with aggregation-induced emission (AIE) have demonstrated superior performance in deeper penetration depth with better resolution, higher signal-to-noise ratio, and lower side effects in the second near-infrared window (NIR-II, 1000–1700 nm) than in any other range. Herein, the latest advances in NIR-II AIE NPs in cancer theranostics are summarized. In particular, we focus on the design of multifunctional AIE agents with both strong NIR-II emission and effective photothermal conversion or reactive oxygen species (ROS) production, as well as their translational biomedical applications, including imaging diagnosis, image-guided surgery, and image-guided phototherapy, etc. At the end of this review, the opportunities and challenges of this field are also discussed.     

Biodegradable Tri-Block Copolymer Poly(lactic acid)-poly(ethylene glycol)-poly(l-lysine)(PLA-PEG-PLL) as a Non-Viral Vector to Enhance Gene Transfection

Low cytotoxicity and high gene transfection efficiency are critical issues in designing current non-viral gene delivery vectors. The purpose of the present work was to synthesize the novel biodegradable poly (lactic acid)-poly(ethylene glycol)-poly(l-lysine) (PLA-PEG-PLL) copolymer, and explore its applicability and feasibility as a non-viral vector for gene transport. PLA-PEG-PLL was obtained by the ring-opening polymerization of Lys(Z)-NCA onto amine-terminated NH₂-PEG-PLA, then acidolysis to remove benzyloxycarbonyl. The tri-block copolymer PLA-PEG-PLL combined the characters of cationic polymer PLL, PLA and PEG: the self-assembled nanoparticles (NPs) possessed a PEG loop structure to increase the stability, hydrophobic PLA segments as the core, and the primary ɛ-amine groups of lysine in PLL to electrostatically interact with negatively charged phosphate groups of DNA to deposit with the PLA core. The physicochemical properties (morphology, particle size and surface charge) and the biological properties (protection from nuclease degradation, plasma stability, in vitro cytotoxicity, and in vitro transfection ability in HeLa and HepG2 cells) of the gene-loaded PLA-PEG-PLL nanoparticles (PLA-PEG-PLL NPs) were evaluated, respectively. Agarose gel electrophoresis assay confirmed that the PLA-PEG-PLL NPs could condense DNA thoroughly and protect DNA from nuclease degradation. Initial experiments showed that PLA-PEG-PLL NPs/DNA complexes exhibited almost no toxicity and higher gene expression (up to 21.64% in HepG2 cells and 31.63% in HeLa cells) than PEI/DNA complexes (14.01% and 24.22%). These results revealed that the biodegradable tri-block copolymer PLA-PEG-PLL might be a very attractive candidate as a non-viral vector and might alleviate the drawbacks of the conventional cationic vectors/DNA complexes for gene delivery in vivo.     

分子模拟方法在环氧树脂研究中的应用

分子模拟方法是一种新型的科学研究的方法,而环氧树脂材料是一类重要的高分子材料。近年来,分子模拟方法被应用于环氧树脂及其固化剂的分子设计中并且引起了极大的关注。笔者根据相关文献从研究的主要问题和方法对分子模拟法在环氧树脂中的应用作一综述。     

CdS量子点作荧光探针检测水相中微量铜的方法研究

用巯基丙酸作为稳定剂,在水相中合成了CdS量子点。基于Cu^2＋对CdS量子点有显著的荧光猝灭作用,建立了检测水相中微量Cu^2＋的新方法。研究结果表明,在弱碱性的水溶液中,当Cu^2＋的浓度在1×10^-5-3×10^-4 mol·L^-1之间时,量子点的荧光猝灭强度△F/F与Cu^2＋的浓度之间很好地符合Stern-Volmer线性方程,线性相关系数为0.9952。方法的检出限为5.85×10^-6 mol·L^-1,相对标准偏差为3.75%,加标回收率为95.5%-118.5%。讨论了量子点的荧光猝灭机理。在研究金属离子和一些化合物的干扰作用时,发现有的物质使量子点的荧光猝灭,有的物质却使量子点的荧光强度增强,发光强度对不同的物质就具有选择性。选择合适的掩蔽剂可以消除较强的离子干扰。     

煤分级炼制清洁燃料系统研究

为了实现碎煤分质清洁高效利用,提出一种煤分级炼制清洁燃料系统。该系统以廉价丰富的碎煤为原料,利用固体热载体回转窑热解技术,将碎煤转化为半焦、焦油和煤气等中间产物,然后经煤气变换、深冷分离、焦油加氢、半焦成型等加工过程,最终生产出石脑油、柴油、液化天然气、洁净煤等清洁燃料产品。以年处理1000万t神东长焰碎煤(25 mm)系统为例进行模拟计算。结果表明:系统每年可生产约618.0万t洁净煤、61.4万t油品和46.0万t液化天然气,原煤增值约3.6倍。通过系统集成与优化,该系统年耗水仅约310万t,能效达到75%以上,废水废固近零排放。在当前市场价格情况下,该系统总投资约125.0亿元,年销售收入约94.1亿元,年创造利税约21.4亿元。投资回收期4~5 a(不含建设期),经济效益显著。     

Study of the hexagonal to monoclinic celsian phase transition induced by magnetic phase nucleation in barium aluminosilicate glass-ceramics

The inert hexagonal to monoclinic celsian (H-M) phase transition extremely restricts the formation of celsian. In this study, Fe³⁺ dopants were incorporated into nonmagnetic barium aluminosilicate (BAS) glass-ceramics using Fe(NO₃)₃.9 H₂O as raw material for preparing the celsian phase. As the Fe-Ba mole ratio reached 0.238, the celsian phase can be obtained in magnetic BAS glass-ceramics. It implied that some magnetic reaction products facilitated the H-M phase transition. To examine the above inference, magnetic barium ferrite (BFO) additions were externally incorporated into a pure BAS glass matrix. Results suggested that BFO additions can significantly promote the H-M phase transition. When the addition of BFO was increased to 5 wt %, almost all of the hexacelsian phase was converted into the celsian phase. And the reason was that barium ferrite can act as a nucleation agent to induce the distorted hexacelsian phase decreasing the H-M phase transition barrier.     

PET Probes for Preclinical Imaging of GRPR-Positive Prostate Cancer: Comparative Preclinical Study of [68Ga]Ga-NODAGA-AMBA and [44Sc]Sc-NODAGA-AMBA

Gastrin-releasing peptide receptors (GRPR) are overexpressed in prostate cancer (PCa). Since bombesin analogue aminobenzoic-acid (AMBA) binds to GRPR with high affinity, scandium-44 conjugated AMBA is a promising radiotracer in the PET diagnostics of GRPR positive tumors. Herein, the GRPR specificity of the newly synthetized [⁴⁴Sc]Sc-NODAGA-AMBA was investigated in vitro and in vivo applying PCa PC-3 xenograft. After the in-vitro assessment of receptor binding, PC-3 tumor-bearing mice were injected with [⁴⁴Sc]Sc/[⁶⁸Ga]Ga-NODAGA-AMBA (in blocking studies with bombesin) and in-vivo PET examinations were performed to determine the radiotracer uptake in standardized uptake values (SUV). ⁴⁴Sc/⁶⁸Ga-labelled NODAGA-AMBA was produced with high molar activity (approx. 20 GBq/µmoL) and excellent radiochemical purity. The in-vitro accumulation of [⁴⁴Sc]Sc-NODAGA-AMBA in PC-3 cells was approximately 25-fold higher than that of the control HaCaT cells. Relatively higher uptake was found in vitro, ex vivo, and in vivo in the same tumor with the ⁴⁴Sc-labelled probe compared to [⁶⁸Ga]Ga-NODAGA-AMBA. The GRPR specificity of [⁴⁴Sc]Sc-NODAGA-AMBA was confirmed by significantly (p ≤ 0.01) decreased %ID and SUV values in PC-3 tumors after bombesin pretreatment. The outstanding binding properties of the novel [⁴⁴Sc]Sc-NODAGA-AMBA to GRPR outlines its potential to be a valuable radiotracer in the imaging of GRPR-positive PCa.