A Flexible Bivalent Approach to Comprehensively Improve the Performances of Stilbazolium Dyes as Amyloid-ß Fluorescent Probes.

Exploring new ways to reconstruct the structure and function of inappropriate organic fluorophores for improving amyloid-ß (Aß) fluorescent imaging performance is desired for precise detection and early diagnosis of Alzheimer's disease (AD). With stilbazolium dyes as examples, here, we present a multipronged approach to comprehensively improved the Aß fluorescent imaging performance through a flexible bivalent method, where a flexible carbon chain was introduced to link two monomers to form a homodimer. Our results reveal a mechanism wherein the flexible linker creates a well-defined probe with specific orientations and distinct photophysical properties. Applying this approach in combination with theoretical simulation, the homodimers exhibited a comprehensive improvement of the Aß fluorescent imaging performance of the dye monomers, including better photostability and higher signal-to-noise (S/N) ratio, higher "off-on" near-infrared fluorescence (NIRF) response sensitivity, higher specificity and affinity to Aß deposits, and more reasonable lipophilicity for blood-brain barrier (BBB) penetrability. The results demonstrate that flexible homodimers offer a multipronged approach to obtaining high-performance NIRF imaging reagents for the detection of Aß deposits both in vitro and in vivo.

Near-infrared irradiation controlled thermo-switchable polymeric photosensitizer against ß-amyloid fibrillation.

Photothermal therapy (PTT) is an emerging paradigm for the degradation of amyloid-ß (Aß) aggregations and has become an effective way of treating Alzheimer's disease (AD). A promising PTT therapeutic option requires control of at least two key functional aspects: controllable photoactivity and specific activation. In this work, a near-infrared (NIR)-activated thermo-switchable biopolymeric PTT agent was designed and synthesized by conjugating a molecular rotor-based boron dipyrromethene photosensitizer (BDP) to a temperature-responsive polymer backbone of biopolymeric hydroxypropyl cellulose (HPC). The as-synthesized BDP-HPC exhibited an ultra-high PCE of 78.1% along with prominent cycling stability of phase-transition behavior under NIR irradiation in the light of the lower critical solution temperature (LCST at 42.5 °C). Importantly, the NIR irradiation can manipulate the reversible phase transition behavior of the resultant BDP-HPC that reveals high effectiveness in inhibiting Aß aggregation together with the obvious ability to dissociate Aß aggregations. Our work reveals an accurate modulation strategy for versatile and high-performance AD treatment.

Phosphorylation of covalent organic framework nanospheres for inhibition of amyloid-ß peptide fibrillation.

The development and exploration of new nanostructural inhibitors against Alzheimer's disease (AD)-associated amyloid-ß (Aß) fibrillation have attracted extensive attention and become a new frontier in nanomedicine. However, focusing on finding an effective nanostructure is one of the most challenging parts of the therapeutics task. Herein, nanoscale spherical covalent organic frameworks (COFs) via post-synthetic functionalization with sodium phosphate (SP) groups on the channel networks were found to efficiently inhibit Aß fibrillation. The as-prepared uniform SP-COF nanospheres with high surface area, good crystallinity, and chemical stability were characterized by multifarious microscopic and spectroscopic techniques. Moreover, molecular dynamics simulation together with fibrillation kinetics and cytotoxicity assay experiments shows that there were restricted-access adsorption channels in the SP-COFs which were formed by the cavities with size and functional groups accommodated to the Aß peptide sequence and significantly affected the fibrillation and cytotoxicity of Aß. Transmission electron microscopy (TEM), dynamic light scattering (DLS) monitoring, isothermal titration calorimetry (ITC), Fourier transform infrared (FT-IR) and circular dichroism (CD) spectra measurements, and confocal imaging observation were performed to understand the inhibition mechanism and influencing factors of the SP-COFs. To our knowledge, our strategy is the first exploration of COF-based anti-amyloidogenic nanomaterials with high affinity and specific targeting, which are crucial for the inhibition of Aß fibrillation for AD prevention and treatment.

Aspartic Acid-Assisted Size-Controllable Synthesis of Nanoscale Spherical Covalent Organic Frameworks with Chiral Interfaces for Inhibiting Amyloid-ß Fibrillation.

Covalent organic framework nanospheres (COF NSs) have garnered special attention due to their uniform sphere morphology, adjustable particle size, and mesoporous microenvironment. However, methods to control an optimal particle size scale while achieving solution dispersibility and specific surface properties remain underdeveloped, which precludes many of the biomedical applications. Here, we propose and develop a general strategy to access simultaneous size control and surface functionalization of uniform spherical COF NSs in a single step using aspartic acid (d-/l-Asp) that plays center roles in an acid catalyst, hydrophilicity, size-controllable synthesis, and chiral enantiomer. In this study, for the first time, we have employed a surface chemistry engineering study to create a variety of nanoscale spherical COFs and subsequently measure parameters to evaluate the effectiveness of Asp in the regulation of the particle size. Moreover, the potential utilization of the d/l-enantiomeric Asp-COF NSs in preventing ß-amyloid (Aß) aggregation is investigated by analyzing their interactions with Aß amyloids using a multitechnique experimental approach. To our knowledge, our strategy is the first synthesis of hydrophilic COF NSs with an optimal length scale and a chiral-selective targeting surface, which are crucial for the inhibition of Aß fibrillation for Alzheimer's disease prevention.

Artificial Chiral Interfaces against Amyloid-ß Peptide Aggregation: Research Progress and Challenges.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by an imbalance between the production and clearance of amyloid-ß (Aß) species. AD not only influences the life quality of the patients but also heavily burdens the families and society. Therefore, it is an urgent mission to research and develop some new anti-amyloid aggregation drugs. In recent years, there were research and development of engineered nanostructures as Aß amyloid inhibitors have attracted extensive attention and become a new frontier in nanomedicine. The effects of nanostructural surface properties (e.g., morphology, charge, hydrophobicity) on inhibition of Aß aggregation are modulated by adsorbed Aß peptides. Nevertheless, chirality has been seldom considered in recognition of Aß species and modulation of Aß aggregations. Moreover, a more relevant question for chiral inhibitors is little known about the molecular mechanism of how to interface chiral effects Aß targeting recognition and effective mitigation of amyloidosis at the molecular level. Herein, we review recent experimental and theoretical results acquired in the specific areas of artificial chiral nanostructure inhibitors. This article will be essential to provide a microlevel insight into the effects of chiral nanointerfaces on amyloidosis processes as well as the development of chiral inhibitor drugs against Aß fibrillation.

Quantitative Analysis of Protein Corona on Precoated Protein Nanoparticles and Determined Nanoparticles with Ultralow Protein Corona and Efficient Targeting in Vivo.

The protein corona on nanoparticles (NPs) is a critical problem that often screens the targeting molecules and becomes one of the key reasons for the lack of practical application in nanotherapy. It is critical to fully understand the mechanism of the nanoparticle-biological interactions to design the nanoparticle-based therapeutic agents. Some types of proteins can be precoated on the nanoparticles to avoid unwanted protein attachment; however, the ultralow level of protein corona is hard to achieve, and the relationship of the antifouling property of the precoated protein nanoparticles with protein conformation and protein-nanoparticle interaction energy has never been investigated. In this work, we provided the quantitative protein corona composition analysis on different precoated protein nanoparticles, and on the basis of the molecular simulation process, we found their antifouling property strongly depended on the interaction energy of the precoated protein-serum protein pair and the number of hydrogen bonds formed between them. Furthermore, it also depended on the nanoparticle-serum protein pair interaction energy and the protein conformation on the nanoparticle. The casein coated nanoparticle with the antifouling property was determined, and after aptamer conjugation and drug loading, they exhibited superior targeting and internalization behavior for photodynamic and photothermal therapy in vitro and in vivo. Our work adds to the understanding of the protein corona behavior of precoated protein nanoparticles, and the determined antifouling NP can potentially be used as a highly efficient nanodrug carrier.

A synergistic approach to enhance the photoelectrochemical performance of carbon dots for molecular imprinting sensors.

Nanoscale carbon dots (CDs) have drawn increasing attention in photoelectrochemical (PEC) sensors for biotoxin detection owing to their many merits including excellent optical, electric and photoelectric properties. In this work, a novel strategy is proposed to improve the photoelectrical response performance of CDs by taking advantage of the synergistic effect of nitrogen and sulfur co-doping and copper phthalocyanine non-covalent functionalization approaches, which rightly adjusts the energy level of CDs, optimization of intimate interfacial contact, extension of the light absorption range, and enhancement of charge-transfer efficiency. This work demonstrates that heteroatom doping and chemical functionalization can endow CDs with various new and improved physicochemical, optical, and structural performances. This synergy contributes enormously to the molecular imprinting photoelectrochemical (MIP-PEC) sensor for toxin detection, and the work typically provided a wide linear range of 0.01 to 1000 ng mL-1 with a detection limit of 0.51 pg mL-1 for ochratoxin A (OTA).

Copper Phthalocyanine-Functionalized Graphitic Carbon Nitride: A Hybrid Heterostructure toward Photoelectrochemical and Photocatalytic Degradation Applications.

In this work, alcian blue 8GX (AB), a copper(II) phthalocyanine derivative, was employed to functionalize graphitic carbon nitride (g-C3 N4 ) for the preparation of a highly efficient photocatalyst. The approach relies on a facile AB-assisted ethanol/water mixed-solvent exfoliation of bulk g-C3 N4 . The as-prepared g-C3 N4 /AB hybrid possesses significantly enhanced solution dispersibility and photoelectrochemical performance resulting from the synergistic effect between g-C3 N4 and AB, which involves the optimization of intimate interfacial contact, extension of light absorption range, and enhancement of charge-transfer efficiency. This synergy contributes enormously to the photocatalytic degradation of rhodamine 6G (R6G) under light irradiation.

Facile Preparation of Bright-Fluorescent Soft Materials from Small Organic Molecules.

Highly fluorescent and biocompatible soft materials are desirable for many potential applications, but their synthetic processes are somehow complicated. Herein, we have explored the feasibility of synthesis of unconventional fluorescence soft materials from small organic molecules under mild conditions. A new blue-fluorescent soft material with high quantum yield (89.6 %) and eutectic feature prepared by simple heat treatment of citric acid (CA) and cysteine (Cys) aqueous mixtures below 100 °C in air was reported. The as-prepared fluorescent material has the features of facile preparation, low cost, scalable production and easy to process, making it suitable for applications like fluorescent labeling and light-emitting devices. This new finding opens a new venue for the preparation of fluorescent soft materials.

Graphene oxide/carbon dot composite: a new photoelectrode material for photocurrent response enhancement.

Low-dimensional carbon nanocomposite-based architectures and anchoring zero-dimensional carbon dots on two-dimensional graphene sheets may provide an important approach to develop energy harvesting and conversion strategies. In this work, as a novel photoelectrode with a high photocurrent response performance based on a composite made with all carbon-based materials consisting of p-type graphene oxide (GO) and n-type nitrogen, sulfur co-doped carbon dot (NS-CD) has been prepared via the electrophoretic deposition approach. The photoelectrochemical measurement shows that the GO/NS-CD composite greatly suppresses the charge recombination and evidently enhances the photocurrent response activity. It is anticipated that this work may pave a valuable step for the further development of all carbon-based optoelectronic devices with excellent performance.

A general solid-state synthesis of chemically-doped fluorescent graphene quantum dots for bioimaging and optoelectronic applications.

Graphene quantum dots (GQDs) have attracted increasing interest because of their excellent properties such as strong photoluminescence, excellent biocompatibility and low cost. Herein, we develop a general method for the synthesis of doped and undoped GQDs, which relies on direct carbonization of organic precursors in the solid state.

Graphene in light: design, synthesis and applications of photo-active graphene and graphene-like materials.

Graphene functionalized with photo-active units has become one of the most exciting topics of research in the last few years, which remarkably sustains and expands the graphene boom. The rise of photo-active graphene in photonics and optoelectronics is evidenced by a spate of recent reports on topics ranging from photodetectors, photovoltaics, and optoelectronics to photocatalysis. For these applications, the fabrication of photo-active graphene through appropriate chemical functionalization strategies is essential as pristine graphene has zero bandgap and only weak absorption of photons. Written from the chemists' point of view, up-to-date chemical functionalization of graphene with various small organic molecules, conjugated polymers, rare-earth components, and inorganic semiconductors is reviewed. Particular attention is paid to the development of graphene functionalized with light-harvesting moieties, including materials synthesis, characterization, energy/charge-transfer processes, and applications in photovoltaics. Challenges currently faced by researchers and future perspectives in this field are also discussed.

Free-radical-promoted conversion of graphite oxide into chemically modified graphene.

The preparation of chemically modified graphene (CMG) generally involves the reduction of graphite oxide (GO) by using various reducing reagents. Herein, we report a free-radical-promoted synthesis of CMG, which does not require any conventional reductant. We demonstrated that the phenyl free radical can efficiently promote the conversion of GO into CMG under mild conditions and produces phenyl-functionalized CMG. This pseudo-"reduction" process is attributed to a free-radical-mediated elimination of the surface-attached oxygen-containing functionalities. This work illustrates a new strategy for preparing CMG that is alternative to the conventional means of chemical reduction. Furthermore, the phenyl-functionalized graphene shows an excellent performance as an electrode material for lithium-battery applications.

Monitoring the layer-by-layer self-assembly of graphene and graphene oxide by spectroscopic ellipsometry.

Thin films of graphene oxide, graphene and copper (II) phthalocyanine dye have been successfully fabricated by electrostatic layer-by-layer (LbL) assembly approach. We present the first variable angle spectroscopic ellipsometry (VASE) investigation on these graphene-dye hybrid thin films. The thickness evaluation suggested that our LbL assembly process produces highly uniform and reproducible thin films. We demonstrate that the refractive indices of the graphene-dye thin films undergo dramatic variation in the range close to the absorption of the dyes. This investigation provides new insight to the optical properties of graphene containing thin films and shall help to establish an appropriate optical model for graphene-based hybrid materials.

Photoactive graphene sheets prepared by "click" chemistry.

Graphene sheets modified by phenylacetylene moieties provide a facile platform for attaching various photoactive functional molecules via"click" chemistry. The produced photoactive graphene materials are well-dispersed in various solvents and show dramatically improved photo-current responses.