EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2023
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IF 6.7
Yihang Wu,Zixiu Liu,Zhenxiu He,Jumei Yi,Xingfang Qiao,Chunbin Tan,Yajing Xing,Yaobo Zeng,Dajian Yang,Junlin Yin,Baomin Fan,Guangzhi Zeng
Ulcerative colitis is a chronic inflammatory disease with a remitting-relapsing clinical course, it has evolved into a global burden given its high incidence worldwide. Cantharidin (CTD) derivatives are a class of compounds whose structures characterized with a 7-oxabicyclo [2.2.1]heptane core. Though potent cytotoxicity CTD and its derivatives showed, their clinical usage as anti-cancer drugs was limited by the toxicity in organs. In order to find new CTD analogues with good activity and lower toxicity, 21 CTD analogues with or without alkynyl substitution at C5 position of 7-oxabicyclo [2.2.1]heptane core were synthesized, some compounds showed better in vitro anti-inflammatory activity compared to CTD and norcantharidin (NCTD). Based on the structure-activity relationship results of in vitro experiment, analogue 3i was chosen for further study. Results from the acute toxicity in mice showed that 3i was hypotoxic with the single-dose MTD (maximum tolerated dose) for oral administration is over 1852 mg/kg, at least 35-fold lower than that of NCTD. Mechanism study indicated that 3i could potently inhibit TNF-α induced activation of NF-κB signaling by down-regulation the expression levels of phosphor- IKK, IκBα , and NF-κB p65 , and alleviated dextran sulfate sodium-induced colitis in mice. This study indicated that CTD analogues with alkynyl substitution at C5 position of 7-oxabicyclo [2.2.1]heptane core is a kind of new compounds with good anti-inflammatory activity and lower toxicity in vivo, and might be used as therapeutic agents for inflammatory diseases.
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ENZYME AND MICROBIAL TECHNOLOGY
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2023
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IF 3.4
Shuaifeng Liu,Meng Zhang,Dengwang Hong,Zemin Fang,Yazhong Xiao,Wei Fang,Xuecheng Zhang
β-Glucosidases with high catalytic activity and glucose tolerant properties possess promising applications in lignocellulose-based industries. To obtain enzymes possessing these properties, a semi-rational strategy was employed to engineer the glucose-stimulating β-glucosidase Bgl2A for high cellobiose hydrolysis activity. A total of 18 mutants were constructed. A22S, V224D, and A22S/V224D exhibited high specific activities of 272.06, 237.60, and 239.29 U/mg toward cellobiose, which were 2.5- to 2.8-fold of Bgl2A. A22S, V224D, and A22S/V224D exhibited increased k cat values, which were 2.7- to 3.1-fold of Bgl2A. A22S and V224D maintained glucose-stimulating property, whereas A22S/V224D lost it. Using 150 g/L cellobiose as the substrate, the amount of glucose produced by A22S was the highest, yielding 129.70 g/L glucose after 3 h reaction at 35 °C. The synergistic effects of the engineered enzymes with commercial cellulase on hydrolyzing cellulose were investigated. Supplemented with the commercial cellulase and A22S, the highest glucose amount of 23.30 g/L was yielded from cellulose with hydrolysis rate of 21.02 %. Given its high cellobiose hydrolysis activity and glucose-stimulating properties, A22S can be used as a component of enzyme cocktail to match mesophilic cellulases for efficient cellulose hydrolysis.
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FOOD CHEMISTRY
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2023
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IF 8.8
Xiaoying Ma,Xiufeng Zhang,Buyue Zhang,Dawei Yang,Hongxia Sun,Yalin Tang,Lei Shi
Microenvironmental indicators in organisms drive the operation of different physiological functions. In contrast, disruption of microenvironmental homeostasis is often closely associated with various pathological processes. A novel dual-response fluorescent probe based on hemicyanine dye ( HT-Bzh ) was designed and synthesized for the detection of HSO 3 − and viscosity changes. The probe not only provides high sensitivity (limit of detection = 0.2526 μM) for the detection of HSO 3 − using the Michael addition reaction, but also allows the observation of fluorescence emission at 528 nm and thus the monitoring of viscosity changes through hindering of the twisted intramolecular charge transfer (TICT) mechanism. Additionally, dual-response probe has been successfully used to image living cells and detect real food samples. As a new designed tool, HT-Bzh shows excellent anti-interference capability and biocompatibility, which makes it have application potential in other biological systems and in-vivo imaging.
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Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 33
·8046-8055
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IF 7
Yujie Gao,Wenxiang Pei,Yang Yang,Mengmeng Li,Hengqiu Sun,Mingchao Chen,Xiaoman Ma,Hui Zhang,Dongming Qi,Jindan Wu
In most circumstances, wounds face the challenges of bacterial invasions and inappropriate inflammatory responses when they lack proper wound management. Endowing dressings with both antibacterial and anti-inflammatory functions is a compelling strategy for resolving the above issues. However, seizing the right moment to change the dressings and providing satisfactory management of wounds are still urgently required. Herein, an antibacterial and anti-inflammatory nanofibrous mat is proposed by encapsulating antibiotic gentamicin sulfate (GS) and anti-inflammatory drug ibuprofen (IB) into nanofibers via a coaxial electrospinning technique and is further decorated with Prussian blue nanocrystals (PBNCs) to enhance anti-inflammatory activity and, more importantly, to monitor bacterial infections and guide dressing changes in a timely manner. Such a nanofibrous mat releases most of the therapeutic drugs within 120 min and reveals excellent antibacterial activity and anti-inflammatory ability. Specifically, it can destroy both Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), as well as conspicuously reduce the production of reactive oxygen species (ROS) and the expression of pro-inflammatory cytokines in macrophages. In addition, the nanofibrous mat can be used for point-of-use diagnosis of living bacteria relying on the naked eye or color analysis, which exhibits the potential of monitoring wound infection and guiding dressing changes promptly. This finding demonstrates the theranostic applications of multifunctional nanofibrous mats in wound healing.
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TALANTA
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2023
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IF 6.1
Yixuan Xu,Changchang Teng,Huiping Dang,Dalong Yin,Lifeng Yan
Stable organic radical molecules have received extensive attention due to their unique electronic structure and photophysical properties, and the highly fluorescent quantum efficiency has great appeal to bioimaging. However, still scarce reports on the application of them on the therapy of tumors, especially theranostics. Here, 3,6-dibromocarbazole modified tris (2,4,6-trichlorophenyl) methane radical (TB) has been synthesized with high NIR fluorescence quantum efficiency, and free radical nanoparticles (NPs) have been prepared using the precursor of the radical doping strategy. The free radical molecule TB and its precursor molecule HTB were mixed in proportion and encapsulated with an amphiphilic polypeptide (PEG-PAsp) to obtain the NPs. The 4% NPs can achieve a high fluorescence quantum efficiency (18.68%) in the NIR region. In addition, the NPs also have a good ability to produce reactive oxygen species (ROS) under either normoxia or hypoxia conditions, which makes it possible for photodynamic therapy (PDT). Interestingly, the NPs also show preferable photothermal ability (PCE = 42.39%) for photothermal therapy (PTT). Both in vitro and in vivo studies reveal that the as-prepared radical NPS show a NIR fluorescence imaging-guided synergistic PTT and type I/II PDT to tumors. It provides new strategies and new clues for the application of free radical molecules in the theranostics of tumors.
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Nanoscale Advances
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2023
·Vol. 6
·期 2
·722-731
·
IF 4.7
Jiaxi Wang,Wenting Chen,Lei Cao,Mengyan Zhou,Yongkang Geng,Yifei Liu,Shushu Ding,Ding-Yi Fu
Hereby, facile-green copper nanoclusters templated by glutathione S-transferase (GST-CuNCs) have been innovatively synthesized via a simple one-pot stirring method at room temperature. The as-prepared nanoclusters exhibited uniform size with satisfactory fluorescence intensity, good stability and low cytotoxicity. Significantly, the fluorescence of the obtained GST-CuNCs could be considerably enhanced by the addition of chlorotetracycline (CTC) rather than other analogues of CTC, which was ascribed to the aggregation-induced enhancement caused by the interaction between CTC and GST. The enhanced fluorescence intensity demonstrated a good linear correlation with the CTC concentration in the range of 30–120 μM (R2 = 0.99517), and the low detection limit was 69.7 nM. Furthermore, the proposed approach showed favorable selectivity and anti-interference toward CTC among prevalent ions and amino acids. Additionally, this nanoprobe was also applied to the quantitative detection of CTC in serum samples with satisfactory outcomes, which demonstrated excellent prospects for practical applications.
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Journal of Materials Chemistry B
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2023
·
IF 7
Ting Chen,Jie Yang,He Zhao,Dajian Li,Xiaoyong Luo,Zhiyu Fan,Biye Ren,Yuepeng Cai,Renfeng Dong
Ferroptosis is a non-apoptotic form of cell death that is dependent on the accumulation of intracellular iron that causes elevation of toxic lipid peroxides. Therefore, it is crucial to improve the levels of intracellular iron and reactive oxygen species (ROS) in a short time. Here, we first propose ultrasound (US)-propelled Janus nanomotors (Au–FeOx/PEI/ICG, AFPI NMs) to accelerate cellular internalization and induce cancer cell ferroptosis. This nanomotor consists of a gold–iron oxide rod-like Janus nanomotor (Au–FeOx, AF NMs) and a photoactive indocyanine green (ICG) dye on the surface. It not only exhibits accelerating cellular internalization (∼4-fold) caused by its attractive US-driven propulsion but also shows good intracellular motion behavior. In addition, this Janus nanomotor shows excellent intracellular ROS generation performance due to the synergistic effect of the “Fenton or Fenton-like reaction” and the “photochemical reaction”. As a result, the killing efficiency of actively moving nanomotors on cancer cells is 88% higher than that of stationary nanomotors. Unlike previous passive strategies, this work is a significant step toward accelerating cellular internalization and inducing cancer-cell ferroptosis in an active way. These novel US-propelled Janus nanomotors with strong propulsion, efficient cellular internalization and excellent ROS generation are suitable as a novel cell biology research tool.
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ACS Nano
·
2023
·
IF 17.1
Cheng Shen,Yachao Li,Zenan Zeng,Yiming Liu,Yini Xu,Kefurong Deng,Beiling Guo,Dongzhe Zou,Liguo Liu,Xiaoyu Liang,Xianghui Xu
Malignant tumors represent a formidable global health challenge, compelling the pursuit of innovative treatment modalities. Oncolytic therapy has emerged as a promising frontier in antitumor strategies. However, both natural agents (such as oncolytic bacteria or viruses) and synthetic oncolytic peptides confront formidable obstacles in clinical trials, which include the delicate equilibrium between safety and efficacy, the imperative for systemic administration with targeted therapy, and the need to counteract oncolysis-induced immunosuppression. To overcome these dilemmas, we have developed biomimetic nanoengineering to create oncolytic bacteria-inspired nanosystems (OBNs), spanning from hierarchical structural biomimicry to advanced bioactive biomimicry. Our OBNs harbor inherent oncolytic potential, including functionalized oligosaccharides mimicking bacterial cell walls for optimal blood circulation and tumor targeting, tumor acidity-switchable decoration for tumor-specific oncolysis, stereospecific tryptophan-rich peptides for robust oncolytic activity, encapsulated tumor immunomodulators for enhanced immunotherapy, and innate multimodal imaging potential for biological tracing. This work elucidates the efficacy and mechanisms of OBNs, encompassing primary tumor suppression, metastasis prevention, and recurrence inhibition. Systemic administration of d-chiral OBNs has demonstrated superior oncolytic efficacy, surpassing intratumoral injections of clinical-grade oncolytic peptides. This work heralds an era in biomimetic engineering on oncolytic agents, promising the revolutionization of contemporary oncolytic therapy paradigms for clinical translation.
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ACS Nano
·
2023
·
IF 17.1
Fan Yang,Dongju Zhao,Meng Cheng,Yining Liu,Ziyao Chen,Jin Chang,Yan Dou
Metabolic reprogramming that senses brain homeostasis imbalances is necessary to drive detrimental microglial polarization, and specific targeting of this process contributes to the flexible control of pathological inflammatory responses in Alzheimer’s disease (AD), displaying distinctive therapeutic benefits. Herein, glutathione-functionalized gold nanocages loaded with the immunosuppressant fingolimod hydrochloride are developed as brain-targeted and microglia-located immunometabolic reprogramming nanomodulators (GAF NPs) for AD management. By virtue of glutathione-mediated transport properties, this nanomodulator can cross the blood-brain barrier and localize to microglia in AD lesions. Through blocking Akt/mTOR/HIF-1α signaling pathways, GAF NPs not only promote the dominated metabolic shift from glycolysis to oxidative phosphorylation under immune activation but also inhibit transporter-mediated glucose overconsumption by microglia. Correlation analysis based on real-time bioenergetic assessment and 18F-labeled fluorodeoxyglucose (FDG) PET reveals that brain glucose utilization and metabolism restored by GAF NP treatment can serve as a sensitive and effective indicator for microglial M1 to M2 polarization switching, ultimately alleviating neuroinflammation and its derived neurodegeneration as well as ameliorating cognitive decline in AD mice. This work highlights a potential nanomedicine aimed at modifying mTOR-mediated immunometabolic reprogramming to halt energy deprivation-induced AD progression.
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Biomaterials Advances
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2023
·
IF 0
Muqing Xu,Anning Chen,Dongxiu Chen,Shengquan Wu,Zhipeng Deng,Hang Wen,Huiling Zhong,Kejin Lu,Jie Tang,Dong Ma,Hongzheng Zhang
Cochlear implantation (CI) is the primary intervention for patients with sensorineural hearing loss to restore their hearing. However, approximately 90 % of CI recipients experience unexpected fibrosis around the inserted electrode arrays due to acute and chronic inflammation. This fibrosis leads to progressive residual hearing loss. Addressing this complication is crucial for enhancing CI outcomes, yet an effective treatment has not yet been found. In this study, we developed a multifunctional dexamethasone (DXM)-loaded polytrimethylene carbonate (PTMC) electrode coating to mitigate inflammatory reactions and fibrosis after CI. This thin and flexible coating could preserve the mechanical performance of the electrode and reduce the implantation resistance for CI. The in vitro release studies demonstrated the DXM-PTMC coating's efficient drug loading and sustained release capability over 90 days. DXM-PTMC also showed long-term stability, high biocompatibility, and effective anti-inflammatory effects in vitro and in vivo . Compared with the uncoated group, DXM-PTMC coating significantly inhibited the expression of inflammatory factors, such as NO, TNF-α, IL-1β, and IL-6. DXM-PTMC coating suppressed fibrosis in rat implantation models for 3 weeks by reducing both acute and chronic inflammation. Our findings suggest that DXM-PTMC coating is a novel strategy to improve the outcomes of CI.
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DIAMOND AND RELATED MATERIALS
·
2023
·
IF 4.1
Baijian Feng,Zihao Chen,Na Li,Yongguang Bi,Fansheng Kong,Zhong Wang,Shaofan Tan
In this work, for the first time, biomass-derived carbon dots (AMP-CDs) with strong water solubility, antioxidant activity and good biocompatibility were synthesized by a one-step microwave method using Allium macrostemon Bunge polysaccharides (AMP) as the main carbon source, L-cysteine as the nitrogen and sulfur source, and phosphoric acid as the phosphorus source. The results showed that sphere-like AMP-CDs with an average particle size of about 2.34 ± 0.49 nm were successfully prepared, with good resistance to salt and photobleaching, and maintained high fluorescence intensity under normal pH conditions in human body. AMP-CDs were highly resistant to 2,2-diphenyl-1-pycrylhydrazyl (DPPH), 2,2′-Azinobis- (3-ethylbenzthiazoline-6-sulphonate) (ABTS) and hydroxyl radical (·OH) with significantly higher scavenging ability than AMP , with IC 50 (μg/mL) of 10.240, 7.265, and 574.730, respectively. In addition, AMP-CDs can be selectively used for the sensitive detection of Cr 6+ with the limit of detection was 5.25 μM, and satisfactory results were obtained for the Cr 6+ recovery experiments of actual environmental samples. In vitro cytotoxicity and hemolytic activity assays showed that AMP-CDs have good biocompatibility and can smoothly enter cells for clear imaging. Therefore, AMP-CDs are likely expected to be applied as a potential antioxidant and metal ion detection probe in the field of drug and food, environmental and biological scenario samples for metal ion detection analysis.
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Journal of Materials Chemistry B
·
2023
·
IF 7
Qi Long,Yuliang Yang,Fangling Liao,Haoting Chen,Dongyue He,Shengliang Li,Li Pengcheng,Weisheng Guo,Yafang Xiao
Photothermal immunotherapy has shown great potential for efficient cancer treatment. However, the immunosuppressive tumor microenvironment forms a heavy barrier for photothermal-induced anti-tumor immunity by inhibiting dendritic cells (DCs) maturation and cytotoxic T cell response. Moreover, the lack of reliable spatiotemporal imaging modalities makes photothermal immunotherapy difficult to guide tumor ablation and monitor the therapeutic outcomes in real time. Herein, we designed a theranostic thermosensitive liposome (PLDD) as a versatile nanoplatform to boost adaptive anti-tumor immunity of photothermal immunotherapy and achieve multiple bioimaging modalities in a real-time manner. The PLDD contains two major functional components: a multifunctional photothermal agent (DTTB) and an immune potentiator STING pathway agonist (DMXAA). Upon irradiation, the heat generated by DTTB induced the immunogenic cell death (ICD) of the tumor and dissociated the structure of thermosensitive liposome to release DMXAA, which ultimately activated the STING pathway and promoted the ICD-induced immune response by increasing DC cells maturation and T cell recruitment. Meanwhile, the DTTB in PLDD displayed excellent second near-infrared (NIR-II) fluorescence and photoacoustic (PA) dual-modal imaging, which provided omnibearing information on the tumor and guided the subsequent therapeutic operation. Therefore, this versatile PLDD with light-triggered promotion of anti-tumor immunity and multiple spatiotemporal imaging profiles holds great potential for the future development of cancer immunotherapy.
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