ANALYTICAL CHEMISTRY
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2017
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IF 6.32
Jinye Niu,Jilin Fan,Xu Wang,Yongsheng Xiao,Xilei Xie,Xiaoyun Jiao,Chuanzhi Sun,Bo Tang
Biological sensors with simultaneous turn-on signals of fluorescence (FL) and chemiluminescence (CL) triggered by one single species are supposed to integrate spatiotemporally resolved FL imaging with dynamic CL sensing into one luminescent assay. Efficiently increased accuracy can be expected based on complementary information simultaneously obtained from two independent modes, which is crucial in disease detection and diagnosis. However, very few examples can be found to date because of the key challenges in the rational design of sensing structures. Herein, aggregation-induced emission (AIE) was employed to develop a novel organic platform TPE-CLA with simultaneous turn-on FL/CL signals specifically modulated by O2•– in cells, which can be attributed to the activation of AIE resulted from the decreasing solubility after recognition. Using imidazopyrazinone (CLA) as the reactive motif and tetraphenylethene (TPE) as FL/CL enhancing skeleton, TPE-CLA is sensitive enough to image native O2•– in Raw264.7 cells and lipopolysaccharide stimulated O2•– in mice. Endogenous O2•– in HL-7702 cells induced by acetaminophen (APAP) was uninterruptedly monitored for 7200 s with CL and the results were further confirmed by FL imaging. Accordingly, TPE-CLA turns out to be a reliable candidate for real-time and continuous monitoring of endogenous O2•– in live cells. The strategy utilizing AIE to accomplish the FL/CL dual detection is expected to extend the application of AIE as reaction-activated biosensors.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2016
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IF 3.994
Dujuan Zhao,Huiyuan Zhang,Shengfeng Yang,Wenxiu He,Yuxia Luan
The main cause of multidrug resistance (MDR) is overexpression of active efflux transporters, such as P-glycoprotein (P-gp). To reverse MDR and improve the chemotherapy effect of paclitaxel (PTX), we propose a new drug delivery system based on mixed micelles constructed with d -α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS) and the mPEG-SS-PTX conjugate with consideration that TPGS is a P-gp inhibitor that can block the cancer cell action of pumping drugs outside of cells and can enhance the anticancer effect. mPEG-SS-PTX is synthesized by conjugating hydrophilic mPEG with a hydrophobic drug, PTX, via a redox-sensitive disulfide bond. The mPEG-SS-PTX conjugate is amphiphilic and can self-assemble in water. Mixed micelles formed by the mPEG-SS-PTX conjugate and TPGS have a low critical micelle concentration (CMC, ∼1.05 × 10 −3 mg/mL) and high drug loading content (∼19.6%). The disulfide bond in the mPEG-SS-PTX conjugate can be broken in cancer cells (a reductive environment) and release PTX to kill cancer cells. In vitro cytotoxicity and cell uptake suggest that mixed micelles can effectively improve the accumulation of PTX in multidrug-resistant MCF-7 cells. Therefore, the present as-prepared mixed micelles very effectively reverse the MDR and enhance the therapeutic effect.
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JOURNAL OF NANOPARTICLE RESEARCH
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2016
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IF 2.101
Zhang Jing,Li Mengfei,Yuan Zhefan,Wu Dan,Chen Jia-da,Feng Jie
Abstract A novel type of stepwise-activable multifunctional peptide-guided prodrug micelles (MPPM) was fabricated for cancerous cells intracellular drug release. Deca-lysine sequence (K 10 ), a type of cell-penetrating peptide, was synthesized and terminated with azido-glycine. Then a new kind of molecule, alkyne modified doxorubicin (DOX) connecting through disulfide bond (DOX-SS-alkyne), was synthesized. After coupling via Cu-catalyzed azide–alkyne cycloaddition (CuAAC) click chemistry reaction, reduction-sensitive peptide-guided prodrug was obtained. Due to the amphiphilic property of the prodrug, it can assemble to form micelles. To prevent the nanocarriers from unspecific cellular uptake, the prodrug micelles were subsequently modified with 2,3-dimethyl maleic anhydride to obtain MPPM with a negatively charged outer shell. In vitro studies showed that MPPM could be shielded from cells under psychological environment. However, when arriving at mild acidic tumor site, the cell-penetrating capacity of MPPM would be activated by charge reversal of the micelles via hydrolysis of acid-labile β -carboxylic amides and regeneration of K 10 , which enabled efficient internalization of MPPM by tumor cells as well as following glutathione- and protease-induced drug release inside the cancerous cells. Furthermore, since the guide peptide sequences can be accurately designed and synthesized, it can be easily changed for various functions, such as targeting peptide, apoptotic peptide, even aptamers, only need to be terminated with azido-glycine. This method can be used as a template for reduction-sensitive peptide-guided prodrug for cancer therapy. Graphical abstract A novel type of stepwise-activable multifunctional peptide-guided prodrug micelles (MPPM) was fabricated for selective drug delivery in cancerous cells. MPPM could be shielded from cells under psychological environment. However, when arriving at mild acidic tumor site, the cell-penetrating capacity of MPPM would be activated by charge reversal of the prodrug micelles via hydrolysis of acid-labile β -carboxylic amides and regeneration of K 10 . The cell-penetrating peptide, K 10 , would enable efficient internalization of MPPM by tumor cells, and the drug would be rapidly released induced by concentrated glutathione and numerous proteases inside the cancerous cells, resulting in the inhibited effect of the cells .
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ORIGINS OF LIFE AND EVOLUTION OF BIOSPHERES
·
2016
·Vol. 47
·期 4
·413-425
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IF 1.141
Zhang Xianlong,Tian Ge,Gao Jing,Han Mei,Su Rui,Wang Yanxiang,Feng Shouhua
Submarine hydrothermal vents are generally considered as the likely habitats for the origin and evolution of early life on Earth. In recent years, a novel hydrothermal system in Archean subseafloor has been proposed. In this model, highly alkaline and high temperature hydrothermal fluids were generated in basalt-hosted hydrothermal vents, where H 2 and CO 2 could be abundantly provided. These extreme conditions could have played an irreplaceable role in the early evolution of life. Nevertheless, sufficient information has not yet been obtained for the abiotic synthesis of amino acids, which are indispensable components of life, at high temperature and alkaline condition. This study aims to propose a new method for the synthesis of glycine in simulated Archean submarine alkaline vent systems. We investigated the formation of glycine from ethanolamine under conditions of high temperature (80–160 °C) and highly alkaline solutions (pH = 9.70). Experiments were performed in an anaerobic environment under mild pressure (0.1–8.0 MPa) at the same time. The results suggested that the formation of glycine from ethanolamine occurred rapidly and efficiently in the presence of metal powders, and was favored by high temperatures and high pressures. The experiment provides a new pathway for prebiotic glycine formation and points out the phenomenal influence of high-temperature alkaline hydrothermal vents in origin of life in the early ocean.
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Pharmaceutics
·
2025
·Vol. 17
·期 3
·376
·
IF 5.5
Yuxing Zhang,Xixi Zou,Qiran Du,Xiaotao Dong,Uday Kumar Chinta,Ruyue Yu,Fei Wu,Tuo Jin
Objectives: Thermo-gelling hydrophilic polymers like PLGA–PEG–PLGA are known as injectable sustained-release depots for biologics, but they face challenges due to the occurrence of severe burst release. This study aimed to develop a strategy to avoid the initial burst release by pre-encapsulating proteins in polysaccharide microparticles through an aqueous–aqueous emulsion mechanism, thereby enhancing therapeutic retention and linear release kinetics.Methods: Five model proteins (G-CSF, GM-CSF, IGF-1, FVIII, BSA) were encapsulated in dextran microparticles, using an organic solvent-free aqueous–aqueous emulsion method. These particles were dispersed in a 23% (w/w) PLGA–PEG–PLGA solution and injected into a 37 °C release buffer to form a gel depot. The in vitro release profiles were quantified using ELISA and MicroBCA assays over 9–42 days. The bioactivity of the proteins was validated using cell proliferation assays (NFS-60, TF-1, MCF-7) and chromogenic kits. The in vivo pharmacokinetics of the FVIII-loaded formulations were evaluated in Sprague–Dawley rats (n = 5/group) over 28 days.Results: Protein-loaded dextran particles retained their structural integrity within the hydrogel and exhibited minimal burst release (≤5% within 30 min vs. >25% for free proteins). Sustained near-linear release profiles were observed for all the proteins, with complete release by day 9 (G-CSF, GM-CSF, BSA) or day 42 (FVIII). Rats administered with the thermal gel with FVIII–dextran particles showed a significantly lower peak plasma concentration (Cmax: 88.25 ± 30.21 vs. 132.63 ± 66.67 ng/mL) and prolonged therapeutic coverage (>18 days vs. 15 days) compared to those administered with the thermal gel with the FVIII solution. The bioactivity of the released proteins remained at ≥90% of the native forms.Conclusions: Pre-encapsulation in dextran microparticles effectively mitigates burst release from thermosensitive hydrogels, while preserving protein functionality.
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PHYCOLOGICAL RESEARCH
·
2018
·Vol. 66
·期 2
·89-99
·
IF 1.275
Yue Song,Jiali Zhao,Juanjuan Chen,Qijun Luo,Rui Yang,Jilin Xu,Haimin Chen,Xiaojun Yan
SUMMARY Lipid metabolites play an important role in understanding the stress physiology of Pyropia haitanensis , and can be used to facilitate development of stress-resistant Pyropia cultivars. Therefore, in this study ultra performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS) and gas chromatography–mass spectrometry (GC–MS) based metabolomics approaches were developed to screen the responses of lipid metabolites such as phospholipids, glycolipids, fatty acids and volatile organic compounds (VOCs) to different heat shock times. A total of 26 potential lipid biomarkers including Lyso-monogalactosyldiacylglycerol (Lyso-MGDG), Lyso-digalactosyldiacylglycerol (Lyso-DGDG), sulfoquinovosylmonoacylglycerols (SQMG), sulfoquinovosyldiacylglycerol (SQDG), diacylglyceryltrimethylhomoserine (DGTS), triacylglycerol (TAG), Lyso-phosphatidicacid (Lyso-PA), Lyso-phosphatidylcholine (Lyso-PC), Lyso-phosphatidylethanolamine (Lyso-PE), Lyso-phosphatidylglycerol (Lyso-PG), phosphatidylglycerol (PG), phosphatidylinositol (PI), and phosphatidylinositol phosphate (PIP) were identified, most of which responded to high temperature by reducing or increasing levels after stimulation for 1 h or 6 h. After times longer than 6 h, the levels of most lipids gradually recovered to the control group levels. Moreover, the balance of lipids and fatty acids transformation was disrupted. Overall, 11 total fatty acids (TFAs), 13 free fatty acids (FFAs) and 29 VOCs were identified during 0–72 h of high temperature stress. The FFAs, especially polyunsaturated C 20 fatty acids and VOCs, showed opposing change trends, indicating the transformation between C 20 fatty acids and VOCs. Overall, this study provides important insights into the metabolic variations of P. haitanensis under different heat shock time and the relationship between the conversion of lipids, fatty acids, and VOCs. The information provided herein will facilitate efficient development and improvement of Pyropia quality by producing cultivars resistant to high temperature.
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SENSORS
·
2025
·Vol. 25
·期 2
·407
·
IF 3.5
Yingzhen Zhang,Jun Xiao,Ruiying Peng,Xueliang Feng,Haimei Mao,Kunming Liu,Zhenzhong Liu,Chunxin Ma
The detection of highly toxic chemicals such as phosgene is crucial for addressing the severe threats to human health and public safety posed by terrorist attacks and industrial mishaps. However, timely and precise monitoring of phosgene at a low cost remains a significant challenge. This work is the first to report a novel fluorescent system based on the Intramolecular Charge Transfer (ICT) effect, which can rapidly detect phosgene in both solution and gas phases with high sensitivity by integrating a benzo[1,2-b:6,5-b’]dithiophene-4,5-diamine (BDTA) probe. Among existing detecting methods, this fluorescent system stands out as it can respond to phosgene within a mere 30 s and has a detection limit as low as 0.16 μM in solution. Furthermore, the sensing mechanism was rigorously validated through high-resolution mass spectrometry (HRMS) and density functional theory (DFT) calculations. As a result, this fluorescent probing system for phosgene can be effectively adapted for real-time, high-sensitivity sensing and used as a test strip for visual monitoring without the need for specific equipment, which will also provide a new strategy for the fluorescent detection of other toxic materials.
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INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
·
2024
·
IF 3.8
Mingzhe Jiang,Hao Tan,Lixin Jiang,Jintang Duan,Xueping Gu,Lianfang Feng,Cailiang Zhang
The anionic ring-opening polymerization of ε-caprolactam (CL) offers significant potential for producing polyamide 6 (PA6). To establish optimal conditions for designing an efficient and continuous PA6 production process, this study examines the anionic polymerization of CL at temperatures above the crystallization point of PA6. The focus is on the effects of the temperature, activator type and concentration, and catalyst concentration on the polymerization process and product characteristics. At 220 °C, the use of bifunctional methylene diphenyl diisocyanate (MDI) as an activator initiates cross-linking reactions, producing insoluble, nonmelting PA6. In contrast, anionic polymerization without an activator prevents gel formation but results in uncontrollably high molecular weights. The introduction of monofunctional N-acetyl caprolactam (AcCL) as an activator eliminates cross-linking reactions at temperatures above 220 °C while allowing precise control of the product’s molecular weight through adjustments in AcCL concentration.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2017
·
IF 3.887
Jilian Wu,Huiyuan Zhang,Xu Hu,Ruiling Liu,Wei Jiang,Zhonghao Li,Yuxia Luan
Clinically, codelivery of chemotherapeutics has been limited by poor water-solubility and severe systemic toxicity. In this work, we developed a new reduction-sensitive mixed micellar system for self-codelivery of doxorubicin (DOX) and docetaxel (DTX). Biodegradable methoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) was coupled with DOX and DTX by a reduction-sensitive disulfide bond, resulting in mPEG-PCL-SS-DOX and mPEG-PCL-SS-DTX, respectively. mPEG-PCL-SS-DOX was mixed with mPEG-PCL-SS-DTX at a mole ratio of 1:1 in water, forming a mixed micellar system. The mixed micelles had a diameter of 223.7 nm and a low critical micelle concentration. Reductive-triggered drug release revealed a “smart” characteristic of the mixed micelles. A cellular uptake and cytotoxicity assay in vitro showed that the mixed micelles could efficiently accumulate in MCF-7 cells and suppress the growth of tumour cells. The proposed reduction-sensitive mixed micelles assembled from amphiphilic prodrugs can be used as a promising drug codelivery system for cancer therapy.
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ANALYTICAL CHEMISTRY
·
2017
·
IF 6.32
Huixia Di,Huiqiao Liu,Mingmin Li,Jin Li,Dingbin Liu
Precise profiling of the sialic acid (SA) expression on the membrane of cancer cells is critical for early identification of cancers and assessment of cancer metastasis. However, the complex physiological environments often result in false positives with currently available imaging technologies. Herein, we have established a background-free surface-enhanced Raman scattering (SERS) imaging platform that allows high-precision profiling of SA expression in cancer cells and differentiation of clinically relevant cancer tissues with various metastasis degrees. Three-dimensional Raman imaging technique provided a deeper insight into visualizing the probe distribution and thus the SA expression at the single-cell level, without destructing the cells. This noninvasive, high-precision imaging technique could favor early diagnosis, staging, and monitoring therapeutic responses of cancers that are highly essential in clinical settings.
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CONSTRUCTION AND BUILDING MATERIALS
·
2025
·
IF 8
Yujie Wang,Xili Yan,Kenan Li,Siqi Li,Tao Ai,Fengrong Shi
Conventional epoxy asphalt is difficult to reuse due to its thermosetting inability to heal and reprocess. In this study, using dimer acid (DA) and zinc acetate (Zn(OAC) 2 ) as curing agent and catalyst, respectively, and the hydroxyl-ester bonds were introduced into the dynamic crosslinking network system of the asphalt, a highly compatible epoxy asphalt DEA with heat recovery performance was designed. On this basis, the effects of different contents of capped hyperbranched polyester HP102 on the mechanical properties, low-temperature properties, and compatibility of DEA were investigated. The results showed that the base asphalt was successfully grafted with hydroxyl and ester groups, and this chemical modification effect reduced the polarity between the asphalt phase and the resin phase, resulting in a notable improvement in the compatibility of DEA compared with commercially available epoxy asphalt. The introduced HP102 improves not only the low-temperature ductility of the material but also its structural presence of -COO- groups, which can be further used to realize the dynamic exchange and reorganization of hydroxyl-ester bonds, which contributes to the modulus relaxation of the material and enhances its mechanical properties and self-healing ability. The highly branched structure of HP102 increases the unoccupied space and undergoes stress relaxation, which contributes to the improvement of the low-temperature ductility of the material. In addition, the cyclic tensile test results show that the mechanical property recovery rate can reach 86.7 % when hot-pressing processed at 180 °C for 5 h, which confirms that the epoxy asphalt under the reversible covalent crosslinking network possesses non-negligible recycling potential, and provides an engineering application reference for the hot-pressing recycling of epoxy asphalt.
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2025
·
IF 4.6
Qiaolin Li,Chen-Yu Zhou,Huiling Wang,Hong-Tao Shao,Shi-Yu Liu
Hepatic carcinoma is one of the most common malignancies with low survival rates due to insufficient therapeutics while early detection of hepatic tumors remains key to reducing mortality of liver cancer. However, current clinical methods are hard to detect pathological changes in early-stage cases while the detection rate of liquid biopsy-based assay is limited. Thus, effective tools for accurate and sensitive detection of hepatic tumors are still in urgent need. To date, fluorescent probes targeting cancer-related biomarkers and cellular environments have attracted intense attention, among which “dual-locked” probes have developed to avoid false-positives and have shown great potential in accurate detection of tumors. Herein, carboxylesterase (CE), a widely expressed serine hydrolase that shows high relevance with hepatic carcinoma progression and tumor-associated cellular viscosity were chosen as co-targets for hepatic tumor targeting probe development. By rational design and construction of a “dual-locked” probe for simultaneously sensing carboxylesterase activity and cellular viscosity, the newly acquired probe DCI-CV displayed high specificity and sensitivity toward CE in both in vitro assays and cell imaging. Most importantly, DCI-CV was successfully applied to imaging subcutaneous and orthotopic transplanted hepatic tumors with high specificity, demonstrating DCI-CV as a potential tool in hepatic tumor detection and related surgical navigation.
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