ADVANCED FUNCTIONAL MATERIALS
·
2026
·
IF 19.9
Tianxing Zhou,Junnian Chen,Xingya Rao,Haifeng Zhang,Huocheng Yang,Menghuan Li,Zhong Luo
Triple-negative breast cancer (TNBC) is a highly invasive malignancy that responds poorly to current standard therapies. Sonodynamic therapy (SDT) can deliver both reactive oxygen species (ROS)-dependent tumor cytotoxicity and immunostimulatory benefits that holds significant promise for TNBC treatment, but its efficacy is blunted by the elevated Indoleamine 2,3-dioxygenase 1 (IDO1)-driven tryptophan (Trp) catabolism in TNBC, which strengthens antioxidant defenses while exacerbating the immunosuppressive tumor microenvironment. Here we develop an ultrasound-activatable sonodynamic amplifier (PMFN) that reprograms TNBC-intrinsic IDO1-dependent Trp catabolism to potentiate remotely controllable sonodynamic ferroptosis-immunotherapy. We first developed Fe(III)-coordinated tetraphenylporphyrin (FeTPP) as a ferrocatalytic sonosensitizer via molecular-dynamics-assisted virtual screening, which was co-formulated with the IDO1 inhibitor Navoximod (NLG919) into cRGD-modified liposomes for TNBC-targeted delivery. Upon ultrasonication, NLG919 blocks Trp-to-kynurenine (Kyn) conversion to suppress the Nrf2-GPX4 antioxidant axis and mitigate regulatory T cells (Tregs)-associated immunosuppression, while FeTPP amplifies ROS stress through a sonodynamic reaction to drive lipid peroxidation. These effects synergistically promoted immunogenic ferroptosis of TNBC cells and relieved immune suppression, thereby enhancing ferroptosis-immunotherapeutic efficacy. In mouse models, PMFN markedly inhibited primary TNBC growth and abrogated metastasis, providing an approach for advancing TNBC treatment in the clinic.
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高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2020
·Vol. 412
·期 26
·7349-7356
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IF 3.637
Li Jun,Wang Man,Fan Yao-Yao,Duan Hui-Ling,Deng Xu,Zhang Zhi-Qi
The application of the dye-labeled fluorescence method in a ligand-RNA interaction assay is a complex and costly process prone to steric hindrance. Fluorescent nanomaterials offer an attractive alternative due to their simple, low-cost synthesis and effective screening properties. Here, CdTe@ZIF-8 core-shell nanocomposites were used as fluorescence signal transducer in the ligand-TAR RNA interaction assay. Different experimental strategies were developed based on the size-selective nature of the CdTe@ZIF-8 nanocomposites. When ligands can quench fluorescence, two assays of fluorescence recovery with TAR RNA and Tat peptide competitive displacement are carried out successively, which can not only distinguish ligands binding to TAR RNA but also screen potential Tat protein antagonists. When ligands cannot quench fluorescence, the mitoxantrone-TAR RNA complex is used in the competitive displacement assay. Ligands that displaced mitoxantrone from the mitoxantrone-TAR RNA complex signaled the interaction with TAR RNA. Eight ligands, including known and unknown TAR RNA-binding ligands, were tested via the above strategies. The results showed that this method was effective at distinguishing the known RNA-binding partner and screening the Tat antagonist from the test ligands. This simple and effective strategy is expected to be suitable for actual drug screening.
Graphical abstract
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高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2017
·
IF 3.255
Danyi Lu,Qian Xie,Baojian Wu
N -glucuronidation is an important pathway for metabolism and disposition of tertiary amines in humans. This reaction is mainly catalyzed by the enzymes UGT1A4 and UGT2B10. However, the metabolic patterns of UGT1A4- and UGT2B10-mediated N -glucuronidation are not fully clear. In this study, we first optimized in vitro reaction conditions for N -glucuronidation by using specific substrates (i.e., trifluoperazine for UGT1A4, cotinine and amitriptyline for UGT2B10). Furthermore, we found that hepatic N -glucuronidation showed significant species differences. In addition, UGT1A4 and UGT2B10 were primarily responsible for N -glucuronidation of many tertiary amines, including asenapine, loxapine, clozapine, chlorpromazine, dothiepin, doxepin, mirtazapine, mianserin, chlorcyclizine, cyclizine, promethazine, cyclobenzaprine, imatinib, retrorsine, strychnine and brucine. In conclusion, this study provides an in vitro assay system for evaluating N -glucuronidation of amines. Also, UGT1A4- and UGT2B10-mediated N -glucuronidation might play significant roles in metabolism and detoxification of tertiary amines in humans.
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高影响因子
PARASITOLOGY
·
2024
·
IF 2.1
Weisi Wang,Jun Li,Wenjing Qi,Ying Chen,Mengxiao Tian,Chuanchuan Wu,Yao Zhang,Yingfang Yu,Shuai Han,Xiumin Han,Liping Duan,Wenbao Zhang
Human alveolar echinococcosis is a hard-to-treat and largely untreated parasitic disease with high associated health care costs. The current antiparasitic treatment for alveolar echinococcosis relies exclusively on albendazole, which does not act parasiticidally and can induce severe adverse effects. Alternative, and most importantly, improved treatment options are urgently required. A drug repurposing strategy identified the approved antimalarial pyronaridine as a promising candidate against Echinococcus multilocularis infections. Following a 30-day oral regimen (80 mg kg−1 day−1), pyronaridine achieved an excellent therapeutic outcome in a clinically relevant hepatic alveolar echinococcosis murine model, showing a significant reduction in both metacestode size (72.0%) and counts (85.2%) compared to unmedicated infected mice, which revealed significantly more potent anti-echinococcal potency than albendazole treatment at an equal dose (metacestode size: 42.3%; counts: 4.1%). The strong parasiticidal activity of pyronaridine was further confirmed by the destructive damage to metacestode tissues observed morphologically. In addition, a screening campaign combined with computational similarity searching against an approved drug library led to the identification of pirenzepine, a gastric acid-inhibiting drug, exhibiting potent parasiticidal activity against protoscoleces and in vitro cultured small cysts, which warranted further in vivo investigation as a promising anti-echinococcal lead compound. Pyronaridine has a known drug profile and a long track record of safety, and its repurposing could translate rapidly to clinical use for human patients with alveolar echinococcosis as an alternative or salvage treatment.
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高影响因子
MICROCHIMICA ACTA
·
2025
·Vol. 192
·期 4
·1-13
·
IF 5.3
Yang Ruo-Yu,Wang Jin-Hua,Yu Zi-Wei,Chen Yun-Ting,Wu Mei-Juan,Huang Pin-Fang,Liu Meng-Meng
A point-of-care testing platform, consisting of smartphone, miniature electrochemical workstation, and screen-printed carbon electrode (SPCE) modified by gold nanoparticle (AuNPs) and multi-walled carbon nanotubes (MWCNTs), is fabricated for the ultrasensitive detection of paclitaxel (PTX) in human serum and injection solution. To enhance conductivity of the sensing system, MWCNTs concentration and AuNPs electrodeposition time were optimized. The AuNPs/MWCNTs effectively increase the working electrode area of SPCE by a factor of 1.46, contributing to improved electrochemical performance. The steps of electrode surface modification and the characterization of AuNPs/MWCNTs/SPCE were investigated by differential pulse voltammetry, impedance spectroscopy, X-ray photoelectron spectroscopy, and scanning electron microscopy. The sensor shows good linearity between current response and PTX concentration in 0.2 M phosphate buffer at pH = 7.4 (0.05–10 μM, with a limit of detection (LOD) of 1.7 nM) and human serum (0.5–30 μM and a LOD of 3.6 nM). The recoveries range from 89.91 to 103.36% and 91.42 to 103.73% in human serum and injection solution, respectively, with satisfactory relative standard deviation. Moreover, the sensor has excellent stability during 8 weeks and exhibits outstanding specificity and reproducibility towards PTX detection, providing a possible option for PTX determination in practical application such as therapeutic drug monitoring and drug quality control. Graphical
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高影响因子
MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Yu Zhong,An-Yang Li,Jun-Bin Dai,Chen Guo,Shan-Shan Chen,Li-Li Su,Qin-Ying Liu,Yang Sun
Sensitive and rapid quantification of chemotherapeutic drug paclitaxel (PTX) in human serum is crucial for enabling personalized dosing and minimizing severe toxicity. In this approach, an ultrasensitive electrochemical sensor was developed via facile one-step deposition method for rapid determination of PTX. The nitrogen-doped carbon quantum dots-multiwalled carbon nanotubes (NCQDs-MWCNT) nanocomposite, which modified on the screen-printed carbon electrode (SPCE), synergistically enhanced the active surface area, boosted the electrical conductivity and improved the detection sensitivity. Under the optimized conditions, the prepared NCQDs-MWCNT/SPCE exhibited good linearity in both 0.2 M phosphate buffer (pH 7.4) and human serum, and the limit of detection (LOD) reached as low as 1.0 nM and 2.3 nM, respectively. Additionally, the developed sensor possessed satisfactory repeatability, long-term storage property and anti-interference capability. The recovery rates were in the range of 107.73–114.05 % in human serum, indicating its accuracy of PTX measurement. In depth, the electrochemical behaviors of PTX at NCQDs-MWCNT/SPCE were examined. Collectively, the proposed ultrasensitive and facile sensor displays potential applications in therapeutic drug monitoring for PTX, facilitating individualized treatment in precision medicine.
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高影响因子
FOOD CONTROL
·
2024
·
IF 5.6
Qiang Hou,Yali Wang,Jian Hu,Jianxiong Zhang,Caihua Zhang,Wang Song,Xuesong Wang,Baiqin Zheng,Xin Zhou
Due to their potential entry into the human body via the food chain, phenothiazine drugs and their metabolites pose specific health hazards, making their detection in edible tissues of paramount importance. In this research endeavor, a highly sensitive multi-residue analytical method has been devised for the detection of phenothiazine drugs and their metabolites in animal-derived food products, utilizing high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). The preparation of samples involved the use of 1% formic acid in acetonitrile as the extraction solvent following sample weighing, with multiple extraction steps diligently performed to ensure optimal outcomes. The sample, post-extraction, was directly introduced into the purification column, yielding significant time savings and rendering the process more environmentally sustainable. This procedural step effectively eliminated interfering substances from the sample matrix, including proteins, salts, and phospholipids. Analysis of the extracted samples was conducted through HPLC-MS/MS, employing an electrospray ionization (ESI) ion source. A comprehensive panel of 20 phenothiazine drugs and their metabolites was successfully resolved within a mere 10-min chromatographic run. A robust linear correlation (R 2 ≥ 0.99) was attained within a judiciously chosen range of concentrations. Method validation was meticulously conducted across multiple animal species, including trout, white shrimp, pork, beef and chicken. The developed analytical method has been effectively deployed for the screening and quantification of phenothiazine drugs in real-world samples sourced from commercial livestock and aquatic products.
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