Latest ArticlesDeveloping precise extracellular vesicles (EVs) labelling techniques with minimal disturbance is of great importance to the follow-up EVs detection and analysis. However, currently available methods such as using probes to conjugate phospholipids or membrane proteins have certain limitations due to EV steric hindrance, dye aggregation, etc. Here, we present a microfluidic platform to enhance EVs' labelling efficiency and improve their detection. This platform provides excellent sample throughput and high-efficiency EV labelling at lower label concentrations with an optimized flowing rate. Flow cytometry analysis (FCM) and cellular uptake results show that EV labelling by utilizing this platform possesses the merits of a higher labelling efficiency with 64.1% relative improvement than conventional co-incubation method and a lower background noise. Moreover, this technique maintains EVs' size, morphology and biological activities. After the recipient cells uptake the EVs treated by the microfluidic platform, the spatial and temporal distribution of EVs in the cells are clearly observed. These results demonstrate that our method holds great potential in efficient labelling of EVs, which is essential to subsequent EV quantification and analysis.
The compatibility of the gate dielectrics with semiconductors is vital for constructing efficient conducting channel for high charge transport. However, it is still a highly challenging mission to clearly clarify the relationship between the dielectric layers and the chemical structure of semiconductors, especially vacuum-deposited small molecules. Here, interfacial molecular screening of polyimide (Kapton) dielectric in organic field-effect transistors (OFETs) is comprehensively studied. It is found that the semiconducting small molecules with alkyl side chains prefer to form a high-quality charge transport layer on polyimide (PI) dielectrics compared with the molecules without alkyl side chains. On this basis, the fabricated transistors could reach the mobility of 1.2 cm2 V−1 s−1 the molecule with alkyl side chains on bare PI dielectric. What is more, the compatible semiconductor and dielectric would further produce a low activation energy (EA) of 3.01 meV towards efficient charge transport even at low temperature (e.g., 100 K, 0.9 cm2 V−1 s−1). Our research provides a guiding scheme for the construction of high-performance thin-film field-effect transistors based on PI dielectric layer at room and low temperatures.
Improving the performance of all-small-molecule organic solar cells (ASM-OSCs) largely depends on the design and application of novel donors with appropriate crystallinity. Extending molecular conjugation is an effective method for regulating molecular stacking and crystallinity. In this work, we successfully designed and synthesized two novel acceptor-donor-donor-donor-acceptor (A-D-D-D-A) type oligomeric donors with three dithieno[2,3-d:2’,3’-d’]benzo[1,2-b:4,5-b’]dithiophene (DTBDT) as the central unit, named as 3DTBDT-Cl and 3DTBDT, depending on with and without chlorine substitution on the thiophene side chains. We found that the introduction of chlorine atoms makes the blend films display stronger crystallinity but with large-scale phase separation morphology and more defects, which eventually leads to a power conversion efficiency (PCE) of only 10.83%, whereas the blend films based 3DTBDT with appropriate crystallinity achieved 13.74% PCE. Compared with 3DTBDT-Cl/L8-BO, the 3DTBDT/L8-BO films exhibited a nanoscale bi-continuous interpenetrating network morphology with a smaller domain size and more suitable crystallinity, which guarantees the corresponding devices obtained more efficient exciton dissociation, efficient charge transport, reduced bimolecular recombination, and performed more balanced carrier mobility. These results demonstrated that regulating the crystallinity of oligomeric donors to obtain the desired phase separation morphology in the blend films could facilitate further improving the performance of ASM-OSCs.
Multifunctional molecules with both optical signal and pharmacological activity play an important role in drug development, disease diagnosis, and basic theoretical research. Aminopeptidase N (APN), as a representative tumor biomarker with anti-tumor potential, still lacks a high-precision theranostic probe specifically targeting it. In this study, a novel quaternity design strategy for APN theranostic probe was developed. This proposed strategy utilizes advanced machine learning and molecular dynamics simulations, and cleverly employs the strategy of conformation-induced fluorescence recovery to achieve multi-objective optimization and integration of functional fragments. Through this strategy, a unique "Off–On" theranostic probe, ABTP-DPTB, was ingeniously constructed to light up APN through fluorescence restoration, relying on conformation-induced effects and solvent restriction. Differ from the common diagnostic probes, the intelligent design with non-substrated linkage makes ABTP-DPTB for long-term in-situ imaging. The fabricated probe was used for detecting and inhibiting APN in various environments, with a better in vitro inhibitory than golden-standard drug bestatin.
Bridged polycyclic lactams are important structural units in organic functional materials, natural products, and pharmaceuticals. A flexible and efficient anion cascade reaction was developed for the preparation of bridged polycyclic lactams from readily available malonamides and 1, 4-dien-3-ones. Various highly substituted bridged polycyclic lactams were synthesized in good to excellent yields by tandem nucleophilic sequences in the presence of BuOK in commercially available EtOH solvent at 60 ℃. Notably, the simple reactions can be run on a gram scale. Mechanistically, bis-Michael addition reaction and hemiaminalization reactions are involved in the tandem transformation.
Nanoemulsions are widely used as advanced pharmaceutical delivery systems in biomedical field, due to their high encapsulation efficiency and good therapy efficacy. Nanoemulsification techniques that produce nanoemulsions with controllable sizes and compositions are promising for creating advanced nanoemulsion systems for pharmaceutical delivery. This review summarizes recent advances on low-energy emulsification techniques for producing nanoemulsions, and the use of these nanoemulsions as advanced pharmaceutical delivery systems and as templates to create drug-loaded functional particles for biomedical application. First, nanoemulsification techniques that utilize elaborate interfacial physics/chemistry and micro-/nano-fluidics, featured with relatively-low energy input, to produce nanoemulsions with controllable sizes and compositions, are introduced. Uses of these nanoemulsions to create nanoemulsion-incorporated milli-particles, drug-loaded nanoparticles and nanoparticle-incorporated microparticles with sizes ranging from several millimeters to sub-10 nm are emphasized. Flexible and efficient use of the nanoemulsions, functional nanoparticles and milli-/micro-particles integrated with nanoemulsions or nanoparticles for advanced pharmaceutical delivery in biomedical field are highlighted, with focus on how the interplay between their sizes and compositions achieve desired pharmaceutical-delivery performances. Finally, perspectives on further advances on the controllable production of nanoemulsions are provided.
Enzyme prodrug therapies (EPTs) have been intensively explored as attractive approaches to selective activation of systemically administered benign prodrugs by the exogenous enzymes or enzymes expressed at the desired target site, thus achieving localized, site-specific therapeutic effect. Many effective strategies (e.g., antibody-, viral-, gene-, as well as polymer-directed EPT) have been developed for enzyme localization to locally activate systemically administered benign prodrugs. Nevertheless, intrinsic limitations (e.g., complex intracellular environment and catalyst instability) make the practical application of EPT strategies a task that presents itself as highly challenging. As a promising alternative to natural enzyme, nanozyme has attracted substantial attention since its discovery in 2007, mainly due to the advantages of robust catalytic activity, high stability, low cost, and facile synthesis. Recently, nanozyme-activated prodrug strategies bring a new opportunity for targeted therapy, referred to as nanozyme-activating prodrug therapies. This review focuses on recently reported nanozyme-activated prodrug strategies, aiming to provide some new insights into the potential applications in site-specific drug synthesis.
Nasopharyngeal carcinoma (NPC), a malignant tumor originating from the nasopharynx, is one of the common malignant tumors of the head and neck. There are significant geographical differences in the incidence of nasopharyngeal carcinoma, with a high incidence in China and Southeast Asian countries. Herein, we designed and synthesized a novel near-infrared fluorescent (NIRF) probe to detect glutathione (GSH) in cellular and tumor environments using semi-naphthofluorescein (SNAFL) as the fluorescent molecular backbone and 2-fluoro-4-nitrobenzenesulfonate as the recognition moiety. Upon reaction with GSH, SNAFL-GSH emitted a fluorescence signal, and its emission wavelength at 650 nm was remarkably enhanced. The results of selectivity experiments indicated that SNAFL-GSH was able to discriminate GSH from Cys, Hcy, and H2S. Moreover, SNAFL-GSH could image both endogenous and exogenous GSH and distinguish normal and cancer cells by fluorescence signal difference. At the cellular level, cisplatin (DDP)-induced ferroptosis and inhibition of proliferation of various NPC cell lines (CNE2, CNE1, 5–8F cells) by erastin combined with DDP were visualized with the help of SNAFL-GSH. In a mouse tumor xenograft model, we successfully employed SNAFL-GSH for the evaluation of the efficacy of erastin combined with DDP in the treatment of NPC. More importantly, the probe could image cancerous tissue sections from NPC patients with an imaging depth of approximately 80 µm. It was foreseen that SNAFL-GSH offered great potential for application in the diagnosis and evaluation of the therapeutic efficacy of NPC, and these results would also provide new ideas for the clinical treatment of NPC.
Passive daytime radiative cooling (PDRC) technology is emerging as one of the most promising solutions to the global problem of spacing cooling, but its practical application is limited due to reduced cooling effectiveness caused by daily wear and tear, as well as dirt contamination. To tackle this problem, we report a novel strategy by introducing a renewable armor structure for prolonging the anti-fouling and cooling effectiveness properties of the PDRC coatings. The armor structure is designed by decorating fluorinated hollow glass microspheres (HGM) inside rigid resin composite matrices. The HGM serve triple purposes, including providing isolated cavities for enhanced solar reflectance, reinforcing the matrices to form robust armored structures, and increasing thermal emittance. When the coatings are worn, the HGM on the surface expose their concave cavities with numerous hydrophobic fragments, generating a highly rough surface that guarantee the superhydrophobic function. The coatings show a high sunlight reflectance (0.93) and thermal emittance (0.94) in the long-wave infrared window, leading to a cooling of 5 ℃ below ambient temperature under high solar flux (~900 W/m2). When anti-fouling functions are reduced, they can be regenerated more than 100 cycles without compromising the PDRC function by simple wearing treatment. Furthermore, these coatings can be easily prepared using a one-pot spray method with low-cost materials, exhibit strong adhesion to a variety of substrates, and demonstrate exceptional environmental stability. Therefore, we anticipate their immediate application opportunities for spacing cooling.
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