Analytical Methods
·
2018
·Vol. 11
·期 4
·443-453
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IF 2.073
Pramod K. Kalambate,Yankai Li,Yue Shen,Yunhui Huang
In this work, a novel highly sensitive electrochemical sensing platform has been developed for simultaneous determination of anticancer drugs doxorubicin (DOX) and dasatinib (DAS) by means of mesoporous Pd@Pt core–shell nanoparticles supported on MWCNT (Pd@Pt/MWCNT). The electrochemical behaviour of the drugs was assessed through cyclic voltammetry, while simultaneous determination was carried out using adsorptive stripping square wave voltammetry (AdSSWV). Under optimized conditions, the method exhibits linear responses towards simultaneous determination of DOX and DAS in the concentration ranges of 4.4–8580 nM and 38–9880 nM, with detection limits of 0.86 and 6.72 nM, respectively. Furthermore, the proposed platform was successfully used for reliable determination of DOX and DAS in urine and blood serum samples with good accuracy and precision. The satisfactory recoveries obtained in blood serum and urine samples showed the potential for application of the proposed platform in quality control in the pharmaceutical industry, clinical analysis and optimization of chemotherapeutic treatment. We found that the established sensor has several advantages in terms of high sensitivity and selectivity, ease of preparation, short analysis time, long-term stability and fast response.
研究领域:
分析化学
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药物分析
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癌症治疗
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高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
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2026
·
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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Bone Research
·
2026
·Vol. 14
·期 1
·82
·
IF 20.1
Huang Tiannan,Wu Shali,Qian Wei,Chen Ruiying,Chen Erman,Wang Meizhu,Zhang Cui,Zhou Chenhe,Yu Luyang,Wu Mengjie,Li Yi-Ping,Wu Mengrui
Exhaustion of skeletal stem and progenitor cells (SSPCs) drives age-related delays in fracture repair, yet the upstream regulators of SSPC maintenance are unclear. We identify that core-binding factor β (Cbfβ) in bone marrow Adipoq + cells (BMACs) is essential for maintaining SSPC number and function. Cbfβ deletion in BMACs (CKO) leads to SSPC depletion, including periosteal populations, and impairs bicortical fracture healing in mice. Multi-omics (RNA-seq, CUT&Tag-seq, and ATAC-seq) reveal that Cbfβ preserves chromatin accessibility at DNA repair loci, maintaining genomic stability, preventing BMAC senescence, and mitigating the senescence-associated secretory phenotype (SASP). Senolytic therapy alleviates BMAC senescence, restores SSPC populations, and improves bone repair in CKO mice. In both humans and mice, Cbfβ expression declines with aging, accompanied by increased BMAC senescence. AAV-mediated Cbfβ overexpression restores aging-related bone repair and SSPC decline. These findings reveal a novel mechanism in which Cbfβ in BMACs regulates SSPC maintenance via a senescence/SASP axis, offering a potential therapeutic strategy for age-related bone repair deficits.
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Science Advances
·
2026
·Vol. 12
·期 13
·
IF 13.9
Jiansong Zhao,Tian Yin,Yaxin Deng,Hongbing Liu,Mingli Wei,Chenxiao Chu,Xinxin Liang,Xiaoshuang Bi,Haibing He,Jingxin Gou,Xing Tang,Yu Zhang
Exosomes, despite their promise as drug carriers for crossing biological barriers, remain underexplored for noninvasive posterior ocular delivery. Here, we demonstrate that semen-derived exosomes (SEVs) penetrate ocular barriers effectively, owing to their epidermal growth factor expression, which mediates reversible tight-junction disruption. SEVs reach the posterior segment via dual corneal and conjunctival routes. Using this, we engineered FA-SEVs@CMG eye drops, where SEVs are modified with folic acid (FA) and loaded with a nanozyme system (CMG) composed of carbon dots, manganese dioxide, and glucose oxidase. This eye drop leverages SEVs’ excellent penetration ability and FA’s targeting effect to enhance drug delivery to retinoblastoma (RB) cells. Internalized CMG induces intense oxidative stress, disrupts the autophagy-apoptosis balance, and triggers RB cell self-destruction. In vivo, FA-SEVs@CMG effectively inhibits RB growth while preserving retinal function. This work establishes the first SEV-based platform for noninvasive posterior segment delivery, offering a transformative strategy for treating posterior ocular diseases.
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CHEMISTRY-A EUROPEAN JOURNAL
·
2025
·
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
Acta Pharmaceutica Sinica B
·
2025
·
IF 14.6
Mengnan Yang,Yuqing Tong,Shaoping Yin,Hengchuan Zhang,Xiaowen Huang,Kai Yuan,Yanfei Hao,Jianping Zhou,Meirong Huo,Tingjie Yin
Local inhibition of the “patching” function of tumor-associated platelets against neutrophil infiltration-caused vascular breaches has been used as an “enhanced permeability and retention (EPR) amplification” strategy. Nevertheless, the vascular leakage-resulted elevation of interstitial fluid pressure (IFP) could impact tumoral perfusion and convection of nanodrugs. Especially for hypoperfused and desmoplastic pancreatic ductal adenocarcinoma (PDAC), solely relying on vascular destruction would predictably diminish tumoral drug perfusion. According to multi-thrombosis formation in PDAC, a microthrombi and matrix co-targeted dasatinib (DAS) nano-micelle (CPHD/DAS) synchronizing endothelial gap opening and matrix decompression was constructed for sustained augmentation of drug perfusion within PDAC. CPHD/DAS was composed of CREKA peptide-modified hyaluronic acid–deoxycholate conjugates co-assembled with DAS. In vitro and in vivo results demonstrated CPHD/DAS not only retarded tumor-associated platelet activation to enhance vascular permeability and expose subvascular matrix, but also inhibited pancreatic stellate cell activation to alleviate stroma barrier. Thus, the matrix decompression resisted IFP elevation caused by endothelial gap opening, facilitating sustained up-regulation of functional vessels. Based on superior tumor accumulation and penetration, CPHD/DAS exhibited favorable potency in Panc02 tumor model. This study provides a paradigm to improve the efficiency and application scope of “EPR amplification” strategy in antitumor therapy.
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JOURNAL OF CHROMATOGRAPHY A
·
2025
·
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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RSC Advances
·
2025
·Vol. 15
·期 40
·33536-33548
·
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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高影响因子
Research
·
2025
·
IF 10.7
Xiaolan Zhou,Xiaofeng Zhu,Weixu Wang,Jing Wang,Haimei Wen,Yuqi Zhao,Jiayu Zhang,Qiushi Xu,Zhaozhao Zhao,Ting Ni
Drug resistance to a single agent is common in cancer-targeted therapies, and rational drug combinations are a promising approach to overcome this challenge. Many Food and Drug Administration-approved drugs can induce cellular senescence, which possesses unique vulnerabilities and molecular signatures. However, there is limited analysis on the effect of the combination of cellular-senescence-inducing drugs and targeted therapy drugs. Here, we conducted a comprehensive evaluation of cellular senescence using 7 senescence-associated gene sets. We quantified the cellular senescence states of ~10,000 tumor samples from The Cancer Genome Atlas and examined their associations with targeted drug responses. Our analysis revealed that tumors with higher cellular senescence scores exhibited increased sensitivity to targeted drugs. As a proof of concept, we experimentally confirmed that etoposide-induced senescence sensitized lung cancer cells to 2 widely used targeted drugs, erlotinib and dasatinib. Furthermore, we identified multiple genes whose dependencies were associated with senescence status across ~1,000 cancer cell lines, suggesting that cellular senescence generates unique vulnerabilities for therapeutic exploitation. Our study provides a comprehensive overview of drug response related to cellular senescence and highlights the potential of combining senescence-inducing agents with targeted therapies to improve treatment outcomes in lung cancer, revealing novel applications of cellular senescence in targeted cancer therapies.
研究领域:
肿瘤学
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分子生物学
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药理学
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PubMed
高影响因子
Nanomedicine-Nanotechnology Biology and Medicine
·
2024
·
IF 4.2
Lisha Liu,Beiyuan Zhang,Xianggui Wu,Gang Cheng,Xiaopeng Han,Xiaofei Xin,Chao Qin,Lei Yang,Meirong Huo,Lifang Yin
Cancer-associated fibroblasts (CAFs) play a crucial role in creating an immunosuppressive environment and remodeling the extracellular matrix within tumors, leading to chemotherapy resistance and limited immune cell infiltration. To address these challenges, integrating CAFs deactivation into immunogenic chemotherapy may represent a promising approach to the reversal of immune-excluded tumor. We developed a tumor-targeted nanomedicine called the glutathione-responsive nanocomplex (GNC). The GNC co-loaded dasatinib, a CAF inhibitor, and paclitaxel, a chemotherapeutic agent, to deactivate CAFs and enhance the effects of immunogenic chemotherapy. Due to the modification with hyaluronic acid, the GNC preferentially accumulated in the tumor periphery and responsively released cargos, mitigating the tumor stroma as well as overcoming chemoresistance. Moreover, GNC treatment exhibited remarkable immunostimulatory efficacy, including CD8+ T cell expansion and PD-L1 downregulation, facilitating immune checkpoint blockade therapy. In summary, the integration of CAF deactivation and immunogenic chemotherapy using the GNC nanoplatform holds promise for rebuilding immune-excluded tumors.
研究领域:
肿瘤学
·
纳米技术
·
免疫疗法
·
药学
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PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2024
·
IF 3.8
Qianqian Wang,Yuanyuan Zheng,Bowen Deng,Di Chen,Liuqun Jia,Nian Shi
This study delineates the development of a novel automated pipette-tip solid-phase extraction (SPE) methodology, employing kapok fiber as a naturally efficient and cost-effective adsorbent for the selective extraction of eleven tyrosine kinase inhibitors (TKIs) from plasma. The uniqueness of this method lies in its assembly, where kapok fibers are ingeniously wrapped around a stainless-steel spring within the pipette tip, ensuring an obstruction-free central space for effortless solution aspiration and dispensation. This design significantly minimizes backpressure, enhancing operational efficiency and ensuring compatibility with pipettors, including the implementation of an electric pipettor to streamline the sample preparation process and facilitate automation. The method's analytical performance, rigorously validated through liquid chromatography-tandem mass spectrometry, exhibits outstanding linearity in ranges of 0.1/0.5–200 ng mL -1 (R² > 0.993), commendable accuracy (86.3%–114.8%), and consistent precision (3.4–11.3%), alongside remarkably low detection limits that span from 0.024 to 0.130 ng mL -1 . The assembly of kapok fiber within the pipette tip, in this unique configuration, results in a practical, cost-effective, eco-friendly, and automated pipette-tip SPE method. This innovation signifies a significant advancement in bioanalytical methodologies, offering an efficient and sustainable approach for extracting analytes from complex biological samples. This process notably enhances both the sensitivity and selectivity of subsequent instrumental analyses.
研究领域:
分析化学
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药物分析
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生物医学工程
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PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Haolin Song,Hongyi Chen,Qinjun Chen,Hongrui Fan,Chufeng Li,Yu Wang,Shilin Zhang,Xuwen Li,Boyu Su,Tao Sun,Chen Jiang
Pancreatic ductal adenocarcinoma (PDAC), one of the most challenging cancers, is uniquely characterized by a biological barrier composed of multiple components in the extracellular matrix, preventing penetration of chemotherapeutic agents and hindering clinical drug treatment. Collagen I arrangement is critical. In this study, gemcitabine is chosen as the chemotherapeutic agent and dasatinib as the collagen-I-disrupting agent. When collagen I arrangement is disrupted, not only the chemotherapeutic drug enters the tumor area better, but the infiltration of CD8 + T cells into the tumor also increases. Therefore, a hypoxia-responsive linker-crosslinked polymer, DGD/L@GBI, is designed, which can be simultaneously loaded with two therapeutic agents, gemcitabine and dasatinib. The polymer is encapsulated by nucleic acid aptamers that target the PDAC stromal microenvironment and shield the surface. The aptamer is removed upon arrival at the PDAC hypoxic microenvironment, exposing the positively charged core to achieve charge reversal. Particle size transformation is achieved using linkers that respond to a hypoxic microenvironment. Increased intratumoral penetration is achieved using the dual transformation capabilities of the formulation. Pairing these two agents can result in a powerful efficacy in chemotherapy sensitization and immune infiltration.
研究领域:
肿瘤学
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药学
·
生物医学工程
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高影响因子
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