Latest ArticlesExcessive mercury ions (Hg2+) in the environment can accumulate in human body along with the food chain to cause serious physiological reactions. The fluorescence probes were considered as convenient tool with great potential for Hg2+ detection. Most existing probes suffer from aggregation-induced quenching (ACQ) effects and insufficient sensitivity. Herein, a novel type of fluorophore was developed by combining the aggregation-induced emission (AIE) and excited state intramolecular proton transfer (ESIPT) characteristics. Subsequently, a phenyl thioformate group with photoinduced electron transfer (PET) effect was connected to give an efficient "turn-on" probe (HTM), which exhibited good selectivity toward Hg2+, short response time (30 min), coupled with extremely low detection limit (LOD = 1.68 nmol/L). In addition, HTM was used successfully in real samples, cells and drug evaluation, underlying the superiority of HTM to detect Hg2+ in practical applications.
Light-responsive carriers have been used for the controlled release of antitumor drugs in recent years. However, most light-responsive vectors require high-energy ultraviolet or visible light to achieve local drug release, and ultraviolet light would cause cellular damage. Near-infrared light has a deeper tissue-penetration depths and minimal harm to tissues, but it is difficult to cleave the chemical bond directly. The aim of this study is to develop a novel near-infrared light-responsive carrier for local release of antitumor drugs. Unsaturated phospholipids can be oxidized by singlet oxygen to achieve liposomal drug release, and singlet oxygen can be produced by photosensitizer under light irradiation. A new near-infrared light-responsive nanoliposome was designed that imparts light-triggered local drug release. Nanoliposomes, which were composed of matrix phospholipids and unsaturated phospholipids, were prepared by ammonium sulfate gradient method, and loaded with antitumor drug doxorubicin (DOX) and photosensitizer 1, 4, 8, 11, 15, 18, 22, 25-octabutoxypalladium phthalocyanine. Under near-infrared light, photosensitizers could produce singlet oxygen and damage tumor cells by photodynamic therapy. Simultaneously, the unsaturated phospholipids were oxidized by singlet oxygen and result in DOX release, causing sustained cell damage by chemotherapy. Near-infrared light-responsive nanoliposomes exhibit enhanced anticancer activity owing to combined treatment of photodynamic therapy and chemotherapy. A new platform is thus offered for designing effective intracellular drug-release systems, holding great promise for future cancer therapy.
Permeation enhancers (PEs), such as N-[8-(2-hydroxybenzoyl)amino]-caprylate (SNAC), have been reported to improve the oral absorption of various macromolecules. However, the bioavailabilities of these formulations are quite low and variable due to the influences of enzymes, pH and other gastrointestinal barriers. In this study, we revealed that SNAC could interact with insulin to form tight complexes in a specific concentration (insulin ≥ 40 µg/mL)-, ratio (SNAC/insulin ≥ 20:1)- and pH (≥ 6.8)-dependent manner, thus contributing to a significantly high efficacy of oral insulin delivery. Specifically, absorption mechanism studies revealed that the SNAC/insulin complexes were internalized into the cells by passive diffusion and remained intact when transported in the cytosol. Furthermore, the complexes accelerated the exocytosis of insulin to the basolateral side, thereby enhancing its intestinal mucosal permeability. Eudragit® S100-entrapped SNAC/insulin microspheres were then prepared and exhibited an apparent permeability coefficient (Papp) that was 6.6-fold higher than that of the insulin solution. In diabetic rats, hypoglycemic activity was sustained for more than 10 h after the microspheres were loaded into enteric-coated capsules. Further pharmacokinetic studies revealed an approximately 6.3% oral bioavailability in both the fasted and fed states, indicating a negligible food effect. Collectively, this study provides insight into the interaction between PEs and payloads and presents an SNAC-based oral insulin delivery system that has high oral bioavailability and patient-friendly medication guidance.
Tumor immunotherapy, especially immune checkpoint blockade (ICB), has revolutionized the cancer field. However, the limited response of tumors to immunotherapy is a major obstacle. Tumor immunogenic cell death (ICD) is a death mode of tumor cells that can promote tumor immunity. ICD can induce strong antitumor immune responses through the ectopic exposure of calreticulin on the plasma membrane surface and the release of the non-histone nuclear protein high-mobility group box 1 (HMGB1), ATP, and interferon (IFN), thus activating an adaptive immune response against dead cell-associated antigens and enhancing the therapeutic effect of tumor immunotherapy. Chemotherapy, radiotherapy, photothermal therapy, magneto-thermodynamics therapy, nanopulse stimulation, and oncolytic virus therapy can all induce a strong antitumor immune response by ICD. In addition, the application of nanotechnology can precisely target drug delivery and improve the efficacy of immunotherapy. Here we introduce the basic concepts and molecular mechanisms underlying the induction of ICD. Then, we summarize and discuss the progress in the application of nanotechnology in immunotherapy to promote ICD. Finally, we attempt to define the challenges and future directions in this area to extend the benefits of ICD to a broader patient population.
There is a critical need to diagnose and monitor the progression of Alzheimer's disease (AD) using blood-based biomarkers. At present, it is believed that tau biomarkers can be utilized to reliably detect AD. Multimodal techniques are highly sought after for AD diagnosis and progression monitoring. For this purpose, we developed a fluorescent peptide nanoparticles (f-PNPs) arrays that is capable of detecting multiple signals simultaneously. The concentration, aggregation stages, and Young's modulus of tau biomarkers could be analyzed by monitoring the changes of multimodal fluorescence intensity, nano-morphological, and nano-mechanical properties of the f-PNPs arrays. Experimental results indicated that, compared to healthy human, the concentration, Young's modulus, and aggregation levels of tau proteins in blood samples of clinically diagnosed AD patients increased continuously with the increase of disease severity. The minimally invasive and multimodal characterization techniques showed high signal-to-noise ratio for AD diagnosis.
Compared with other transition metal Mxene derived quantum dots (MQDS), Ta-based Mxene quantum dots have good functionality, but Ta-based Mxene quantum dots and their applications have not been studied so far. In this paper, we report for the first time the synthesis of high fluorescence quantum yield (QY) N-doped Ta4C3 quantum dots (N-MQDs) using Ta4C3 quantum dots in acid reflux damaged Ta4C3 nanosheets as precursors and ethylenediamine as nitrogen source. The prepared N-MQDs have excellent blue photoluminescence (PL) properties, particle size is only 2.60 nm, QY is up to 23.4%, and good stability. In addition, it has been reported that N-MQDs can be used as fluorescent probe for detection of Fe3+ and remote force sensing analysis In liquid ion sensing, N-MQDS shows a unique selective quenching of Fe3+ with a detection limit as low as 2 μmol/L, and has great potential as a fast and super-sensitive fluorescent probe for the detection of heavy ion. More importantly, in solid mechanics sensing, the introduction of N-MQDs into self-healing hydrogels can be developed into a fluorescent hydrogel that can be used for accurate remote force measurement and applied in the field of mechanical sensing analysis. Therefore, Ta-based N-MQDs show excellent potential in the field of fluorescence sensing, which provides a door for multi-dimensional sensing of new materials in the future.
Listeriosis is caused by Listeria monocytogenes (LM) and is currently considered to be one of the leading food-borne diseases worldwide, with mortality rate of 20%~30%. Currently, detection methods for LM are time-consuming with low sensitivity, and delayed detection results. SYTO9 has a high affinity for DNA and exhibits enhanced fluorescence upon binding. Therefore, this study used SYTO9 staining and image processing to develop a rapid loop mediated isothermal amplification (LAMP) detection method for LM. Smartphone was successfully used for detecting the color change in different concentrations of LM. Besides, the optimized LAMP reaction temperature was 63 ℃ by color identification, and the limit of detection for LM was 6 copies/µL in the green channel. So, the developed method, based on image processing, is simple, sensitive and rapid, which provides a new idea and method for rapid detection of LM and other food-borne bacterial pathogens.
Nowadays, there are still many challenges to skin regeneration. As a new type of skin substitute, hydrogel has emerging gradually with its excellent properties. However, it is still a challenge to combine with biological active agents to facilitate skin regeneration. Under the circumstance, we synthesized arginine-based poly(ester amide) (Arg-PEA) and hyaluronic acid (HA-MA), and combined them into new hybrid hydrogels via photo-crosslinking. We found that the internal structure and physicochemical properties of hybrid hydrogels were greatly improved with the increase of content of Arg-PEA. Therefore, we designed hybrid hydrogels with 5 wt% and 10 wt% of Arg-PEA content, respectively. Besides, we selected the corresponding anti-inflammatory (CRP, TNF-α) indicators to detect the anti-inflammatory properties of the hybrid hydrogels at the protein level, and the corresponding antioxidant indicators (SOD, GSH/GSSG, MDA) were selected to investigate the antioxidant properties of hybrid hydrogels at the cellular level in vitro. In addition, we also selected relevant genes to test the effect of hybrid hydrogels on fibrosis and vascularization in the process of skin wound healing in vitro and verified them in vivo with a mouse dorsum wound model. The results confirmed that Arg-PEA/HA-MA (AH) hybrid hydrogel was a prospective scaffold material for skin regeneration.
Novel aggregation-induced charge transfer (CT) emission systems with long luminescence lifetime directed by supramolecular strategy have been successfully developed in water. The dimethylacridine-based electron donor (BrAc) with excellent aggregation ability can co-aggregate with a triazine-based electron acceptor (TRZ) to form nanorods in water, which exhibit CT emission with long lifetime (τ = 0.92 µs). As for a similar electron donor (QaAc) with poor aggregation ability, water-soluble pillar[5]arene (WP5) can be introduced to promote the aggregation process, leading to the obvious CT emission with long lifetime (τ = 0.61 µs). In addition, structural modification of the acceptor with substituent groups possessing stronger electron-accepting capabilities will cause red-shift (about 50 nm) of the emission, which allows conveniently constructing long lifetime organic luminescent materials with different emission colors.
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