CHEMISTRY-A EUROPEAN JOURNAL
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2025
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IF 3.7
Gankun Yuan,Ruyue Yang,Wenjing Wen,Zhaoyi Wei,Meiru Song,Lingyang Zhang,Kun Hou,Gaofeng Liang
Graphical Da-CD@CET@CQ NPs can accurately target tumor cells, and the ER-targeting photosensitizer CET can be used as an ICD inducer for amplifying the ICD effect. Meanwhile, the ER PDT was further strengthened by autophagy inhibition, which can achieve more effective autophagy-regulated photodynamic synergistic immunotherapy for triple-negative breast cancer. Activating immunogenic cell death (ICD) represents a promising therapeutic strategy for tumor immunotherapy. However, photodynamic therapy (PDT)-mediated ICD effect is severely limited due to the extremely short half-life and limited diffusion radius of reactive oxygen species (ROS), hindering effective endoplasmic reticulum (ER) stress induction. In addition, targeted therapy of triple-negative breast cancer (TNBC) remains hugely challenging due to the lack of expression of multiple receptors. Herein, we constructed a hierarchical targeting and controllable intelligent nanodelivery material Da-CD@CET@CQ based on poly- β -cyclodextrin with remarkable solubility and stability, loaded with a novel photosensitized ICD inducer, CET, and autophagy inhibitor chloroquine (CQ). Excitingly, Da-CD@CET@CQ NPs can accurately recognize TNBC tumor cells under the mediation of SRC protein. Moreover, CET could achieve observable enrichment in the ER and amplify the ICD effect by in situ ER PDT, which is further strengthened by the autophagy inhibition caused by CQ. All results show that Da-CD@CET@CQ NPs exhibited excellent targeting ability to tumor cells and ER and effectively enhanced synergistic immunotherapy of in situ ER PDT combined with autophagy inhibition, which significantly inhibited tumor growth and metastasis. Overall, our study provides a novel strategy and meaningful guideline for targeted-PDT-synergistic immunotherapy of TNBC.
研究领域:
肿瘤学
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免疫学
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药剂学
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高影响因子
RSC Advances
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2025
·Vol. 15
·期 40
·33536-33548
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IF 4.6
Xiaofei Zhang,Mengyuan Lv,Yuyang Wang,Nan Zhang,Di Chen
Tyrosine kinase inhibitors (TKIs) are critical in cancer therapy, but their clinical application is complicated by narrow therapeutic windows and significant interpatient variability in pharmacokinetics. To address this, this study presents an effective pipette-tip solid-phase microextraction (PT-μSPE) method using kapok fiber-derived biochar (KFB) as a green and cost-effective sorbent for the extraction of TKIs in plasma. The KFB was incorporated as an inner-wall coating within a standard pipette tip, minimizing backpressure and enhancing automation compatibility. This PT-μSPE method is optimized for efficiency and sensitivity, with ethanol used as the desorption solvent. The method is coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the determination of TKIs, demonstrating excellent linearity (R2 > 0.99), sensitivity (LOD: 0.022–0.125 ng mL−1), and reproducibility. Furthermore, the method exhibits notable green chemistry characteristics, including minimal solvent usage and environmental sustainability. The proposed method offers a practical, scalable solution for TKI quantification for potential clinical and pharmacokinetic studies, with potential for high-throughput integration into automated systems.
研究领域:
肿瘤学
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药物代谢
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分析化学
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临床药理学
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转化医学
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环境可持续性
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生物医学分析
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JOURNAL OF CHROMATOGRAPHY A
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2025
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IF 4
Dong Wang,Mengrong Li,Tingting Dai,Xiangyu Zhang,Di Chen
Accurate quantification of tyrosine kinase inhibitors (TKIs) in plasma is essential for therapeutic drug monitoring (TDM). This study presents a novel solid phase extraction (SPE) method employing hydrophobic polypropylene fabric (PPF)—a fibrous material derived from oil-absorbent pads—as the sorbent. The PPF-SPE device was prepared by directly packing fluffed PPF into syringe barrels, eliminating the need for sieve plates and simplifying column assembly. Integrated with liquid chromatography-tandem mass spectrometry (LC-MS/MS), the method enabled sensitive determination of eight clinically relevant TKIs (afatinib, alectinib, ceritinib, dasatinib, sunitinib, pazopanib, tamoxifen, and ibrutinib) in plasma. Key parameters, including PPF amount, sample pH, and desorption conditions, were systematically optimized, yielding high extraction recoveries (83.1–96.4 %) and good reproducibility (RSDs<5.5 %). The method showed excellent linearity (R²>0.99), low detection limits (0.017–0.055 ng/mL), and high intra-/inter-day recoveries (85.1 %–102.6 %) and precision (RSDs<5.3 %). Its practical applicability was validated in spiked plasma under a single-blind design, yielding relative errors of –8.2 % to 5.4 %. Compared to traditional SPE methods, PPF-SPE offers significant advantages in operational simplicity, cost-effectiveness, high throughput, and environmental sustainability.
研究领域:
分析化学
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药物分析
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临床化学
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质谱分析
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2026
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IF 3.8
Wang Dong,Li Mengrong,Zhang Xiangyu,Chai Shiwei,Chen Di
A novel ultrasound-assisted magnetic sorbent–wrapped stick dip extraction (UA-MSWS-DE) method was developed for the batch-scale determination of seven tyrosine kinase inhibitors (TKIs) in human plasma. The extraction device was fabricated by immobilizing octadecylphosphonic acid–functionalized magnetic nanoparticles onto flame-sealed glass capillaries embedded with magnets. Ultrasonic-assisted dip extraction was used to extract TKIs from diluted plasma, followed by quantification via liquid chromatography–tandem mass spectrometry (LC-MS/MS). Key extraction parameters were systematically optimized, yielding the following optimal conditions: sample pH 5.0 and volume 1.0 mL, sorbent particle size 20 nm and dosage 10 mg, extraction time 20 min, and desorption with 150 µL of ethanol for 8 min. The method demonstrated excellent linearity ( R 2 ≥ 0.99), low limits of quantification (0.1–5.0 ng/mL), and good intra-/inter-day precision (RSDs < 14.95%). The accuracy in blinded plasma samples, tested at 0.25–25% of the studied concentration range, ranged from 87.13 to 112.33%. Compared to conventional magnetic dispersive solid-phase extraction, the UA-MSWS-DE strategy simplifies handling and is designed to facilitate potential parallel processing using only an ultrasonic bath. Five greenness metrics confirmed the method’s high sustainability. Furthermore, the modular design enables adaptation to other analytes by modifying the sorbent coating, making UA-MSWS-DE a sensitive, green, and automation-ready method for therapeutic drug monitoring. Graphical
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ANALYTICAL BIOCHEMISTRY
·
2023
·
IF 2.9
Yao Liu,Zhichao He,Heng Liang,Minzhen Han,Jinxingyi Wang,Qian Liu,Yanping Guan
Rapidly developing UHPLC-MS/MS bioassays with high throughput and quality are challenging yet desired in routine clinics. Methods & results A high-throughput UHPLC-MS/MS bioassay has been built for simultaneously quantifying gefitinib , ruxolitinib , dasatinib , imatinib , ibrutinib , methotrexate , cyclophosphamide and paclitaxel . After the protein precipitation with methanol, samples were separated on an Acquity BEH C 18 column following a gradient elution system with methanol and 2 mM ammonium acetate in water at 40 °C with a run time of 3 min (flow rate 0.4 mL/min). Mass quantification in the positive ion SRM mode was then performed with electrospray ionization . The method of specificity, linearity, accuracy, precision, matrix effects, recovery, stability, dilution integrity and carryover were all validated as per the guideline of the China Food and Drug Administration whose values met the admissible limits. Application of the bioassay to therapeutic drug monitoring revealed important variability in the studied anti-tumour drugs. Conclusion This validated approach was shown to be reliable and effective in clinical management, being a valuable support in therapeutic drug monitoring and subsequent individualized dosing optimization.
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2026
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IF 5.6
Chao Zhang,Huai Lan,Liming Yu,Jikai Zhao,Tao Huang,Boxuan Sun,Shan Meng,Jinfeng Duan,Jing Liu,Zijun Zhou,Zhishang Wang,Jiahui Li,Xinyi Huang,Huishan Wang
First to report that radiation-induced atrial fibrillation is driven by cellular senescence. • The GATA4-NF-κB-SASP axis is the key signaling pathway mediating this process. • Senolytic therapy with D/Q (Dasatinib+Quercetin) rescues atrial remodeling and reduces AF susceptibility. • Targeting senescence with senolytics offers a promising strategy to prevent radiation-induced AF. Radiation-induced heart disease is a well-recognized complication of thoracic radiotherapy, with atrial fibrillation (AF) being a particularly notable sequela. The mechanisms by which ionizing radiation (IR) heightens susceptibility to AF remain inadequately understood. This study seeks to elucidate the role of cellular senescence and the GATA4-NF-κB signaling pathway in radiation-induced atrial remodeling and the pathogenesis of AF. An in vivo mouse model was developed through localized cardiac irradiation using 20 Gy X-rays. The irradiated mice demonstrated dose-dependent atrial structural and electrophysiological remodeling. Transcriptomic analysis revealed significant enrichment in DNA damage response (DDR), NF-κB signaling, and aging-related pathways. IR exposure induced substantial DNA damage, activated ATM/ATR pathways, and enhanced autophagic flux. These responses culminated in the accumulation of GATA4 and phosphorylation of NF-κB, which drove the expression of the senescence-associated secretory phenotype (SASP), coinciding with increased senescence-associated β-galactosidase (SA-β-gal) activity. In vitro , these crucial findings were recapitulated using irradiated HL-1 atrial cardiomyocytes, whereas the knockdown of GATA4 effectively suppressed both cellular senescence and SASP expression. Notably, treatment with the senolytic combination of dasatinib and quercetin (D/Q) alleviated DNA damage, inhibited excessive autophagy, and suppressed the GATA4-NF-κB pathway in irradiated mice, thereby reducing SASP levels. These improvements resulted in the reversal of atrial structural and electrophysiological remodeling and a marked reduced susceptibility to AF. Overall, our findings demonstrate that IR promotes atrial remodeling by inducing DNA damage-mediated cellular senescence via the GATA4-NF-κB-SASP axis. Targeting this pathway with senolytics such as D/Q thus identifies a promising therapeutic strategy for preventing radiation-induced atrial fibrillation.
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ANALYTICAL CHEMISTRY
·
2023
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IF 7.4
Zhiming Wang,Jing Tan,Mengxuan Li,Can Gao,Wenwen Li,Jing Xu,Changchuan Guo,Zhenzhen Chen,Rong Cai
Adenosine triphosphate (ATP) is the major energy carrier in organisms, and there are many cellular proteins that can bind to ATP. Among these proteins, kinases are key regulators in several cell signaling processes, and aberrant kinase signaling contributes to the development of many human diseases, including cancer. Hence, small-molecule kinase inhibitors have been successfully used for the treatment of various diseases. Since the ATP-binding pockets are similar for many kinases, it is very important to evaluate the selectivity of different kinase inhibitors. We report here a clickable ATP photoaffinity probe for the global profiling of ATP-binding proteins. After incubating the protein lysate with the ATP probe followed by ultraviolet (UV) irradiation, ATP-binding proteins were labeled with an alkyne handle for subsequent biotin conjugation through click chemistry. Labeled proteins were enriched with streptavidin beads, digested with trypsin, and analyzed using liquid chromatography–tandem mass spectrometry (LC-MS/MS). More than 400 ATP-binding proteins, including approximately 200 kinases, could be identified in a single LC-MS/MS run in the data-dependent acquisition mode. We then applied this method to the analysis of targets of three selected ATP-competitive kinase inhibitors. We were able to successfully identify some of their reported target proteins from label-free quantification results and validated the results using Western blot analyses. Together, we developed a clickable ATP photoaffinity probe for proteome-wide profiling of ATP-binding proteins and demonstrated that this chemoproteomic method is amenable to high-throughput target identification of kinase inhibitors.
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LIFE SCIENCES
·
2021
·
IF 5.037
Dawei Yang,Xiaoyu Tian,Yuchen Ye,Yin Liang,Jie Zhao,Tao Wu,Na Lu
Senescent cancer cells contribute to tumor refractoriness. The removal of senescent cells after chemotherapy prevents or delays cancer relapse. Our study showed that GL-V9 (5-hydroxy-8-methoxy-2-phenyl-7-(4-(pyrrolidin-1-yl) butoxy)-4-H-chromen-4-one), a potential anticancer drug, eliminated senescent MEFs (Mouse embryonic fibroblasts) and drug-induced senescent breast cancer cells. GL-V9 induced apoptosis in senescent MDA-MB-231 cells. Mechanistically, it alkalized lysosomes and increased the abundance of mitochondria as well as ROS (Reactive oxygen species). The senolytic effect of GL-V9 was also observed in epirubicin-treated mammary tumors in MMTV-PyMT mice. Our data thus indicated that GL-V9 is a promising senolytic drug which could be used to improve the outcome of cancer chemotherapy.
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TALANTA
·
2020
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IF 5.339
Yue-Yue Chang,Hai-Long Wu,Huan Fang,Tong Wang,Yang-Zi Ouyang,Xiao-Dong Sun,Gao-Yan Tong,Yu-Jie Ding,Ru-Qin Yu
Three intelligent chemometric multi-way calibration methods including alternating trilinear decomposition (ATLD), alternating trilinear decomposition assisted multivariate curve resolution (ATLD-MCR) and multivariate curve resolution-alternating least squares (MCR-ALS) combined with high performance liquid chromatography-diode array detection (HPLC-DAD) were used to quantify ten molecular targeted anti-tumor drugs in three complex biological matrices (plasma, urine and cell culture media matrices). All analytes can be successfully eluted in 6.5 min. In this experiment, various degrees of time shifts occurred in different samples. While slight time shifts exist in the chromatographic analysis , satisfactory results can be obtained by the three proposed methods. When the time shift was large (5.6 s), the average spiked recoveries obtained by ATLD analysis were in the range of 58.9%–116.5%, which was less than satisfactory. However, the average recoveries obtained by MCR-ALS and ATLD-MCR analysis were 89.8%–114.8% and 84.5%–106.1% respectively, and more satisfactory results were obtained. For further research, ATLD-MCR and MCR-ALS methods were compared, and the results were evaluated by statistical tests. Accuracies of concentrations obtained by them were considered to be no significant difference. In addition, compared with other methods currently published, the proposed chemometric methods combined with the HPLC-DAD can rapidly, simultaneously and accurately determine varieties of molecular targeted anti-tumor drugs in different complex biological matrices even in the presence of severe peak overlaps, severe time shifts, slight baseline drifts and different unknown background interferences.
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JOURNAL OF SEPARATION SCIENCE
·
2021
·Vol. 44
·期 21
·3914-3923
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IF 3.645
Zhao-Yang Wang,Hai-Long Wu,Yue-Yue Chang,Tong Wang,Wei Chen,Gao-Yan Tong,Ru-Qin Yu
An intelligent chemometric second-order calibration method called alternating trilinear decomposition- assisted multivariate curve resolution combined with high-performance liquid chromatography–diode array detection was used for the simultaneous quantification of nine tyrosine kinase inhibitors in three complex biological systems. The method allows simultaneous quantification of the components in different biological matrices without the need for cumbersome pre-treatment steps, complex elution conditions, and complete peak separation. Even with the varying time shift, severe peak overlap, and various unknown interferences, the proposed method can extract pure chromatographic and spectroscopic information for each analyte, while providing accurate qualitative and quantitative results of nine common tyrosine kinase inhibitors in three different biological matrices. All the drugs were eluted in 7 min. The results showed that the nine drugs in each matrix showed good linearity ( r > 0.984) in the calibration range with a root mean square error of calibration less than 0.9 μg/mL. The average spiked recoveries of the target analytes were all in the range of 83.4–110.0%, with standard deviations less than 9.0%. Finally, the classical method was used to validate the proposed method. In comparison to the traditional method, the proposed strategy is accuracy, simultaneous, and interference-free.
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International Journal of Biological Sciences
·
2021
·
IF 6.582
Deng-Pan Wu,Yan Zhou,Li-Xiang Hou,Xiao-Xiao Zhu,Wen Yi,Si-Man Yang,Tian-Yu Lin,Jin-Lan Huang,Bei Zhang,Xiao-Xing Yin
Tamoxifen (TAM) resistance has indicated a significant challenge during endocrine therapy for hormone-sensitive breast cancer. Thus, it is significant to elucidate the molecular events endowing TAM resistance to endocrine therapy. In this study, we found that epithelial-mesenchymal transition (EMT) was an important event to confer TAM resistance, and attenuating EMT by elevating connexin (Cx) 43 expression could reverse TAM resistance. Specifically, Cx43 overexpression improved TAM sensitivity, while Cx43 depletion facilitated TAM insensitivity by modulating EMT in T47D TAM-resistant and -sensitive cells, and transplanted xenografts. Importantly, we found a novel reciprocal regulation between Cx43 and c-Src/PI3K/Akt pathway contributing to EMT and TAM resistance in breast cancer. Moreover, we identified that Cx43 deficiency was significantly correlated with poor relapse-free survival in patients undergoing TAM treatment. Therefore, Cx43 represents a prognostic marker and an attractive target for breast cancer treatments. Therapeutic strategies designed to increase or maintain Cx43 function may be beneficial to overcome TAM resistance.
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