MICROCHEMICAL JOURNAL
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2025
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IF 5.1
Dong Wang,Mengrong Li,Tingting Dai,Xiangyu Zhang,Di Chen
A rapid, sensitive, and green sample preparation method based on polypropylene fiber-supported liquid-phase microextraction followed by liquid chromatography–tandem mass spectrometry was developed for the determination of tyrosine kinase inhibitors in plasma. Commercial oil absorbent pads composed of polypropylene fibers were used to support n-octanol as the extraction phase. The high chemical purity of the polypropylene fiber minimized background interference, enabling reliable trace-level analysis. The in-syringe format allowed simple push–pull operation, and extraction conditions were optimized for maximum efficiency. The method demonstrated excellent linearity (R 2 > 0.995), low limits of quantification (0.067–3.0 ng/mL), and high precision, with intra- and inter-day recoveries ranging from 79.5 % to 113.6 % and relative standard deviations below 14.2 %. A blinded spiked sample analysis confirmed the method’s reliability for clinical application. The greenness of the method, as evaluated by five green assessment tools, demonstrated excellent environmental compatibility. Overall, the proposed in-syringe polypropylene fiber-supported liquid-phase microextraction method offers a simple, cost-effective, and environmentally sustainable solution for the analysis of tyrosine kinase inhibitors in complex biological matrices.
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
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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Science Advances
·
2023
·Vol. 9
·期 50
·
IF 13.6
Lin Su,Dongdong Jin,Yuqiong Wang,Qinglong Wang,Chengfeng Pan,Shuai Jiang,Haojin Yang,Zhengxin Yang,Xin Wang,Neng Xia,Kai Fung Chan,Philip Wai Yan Chiu,Joseph Jao-Yiu Sung,Li Zhang
The magnetic microrobots promise benefits in minimally invasive cell-based therapy. However, they generally suffer from an inevitable compromise between their magnetic responsiveness and biomedical functions. Herein, we report a modularized microrobot consisting of magnetic actuation (MA) and cell scaffold (CS) modules. The MA module with strong magnetism and pH-responsive deformability and the CS module with cell loading-release capabilities were fabricated by three-dimensional printing technique. Subsequently, assembly of modules was performed by designing a shaft-hole structure and customizing their relative dimensions, which enabled magnetic navigation in complex environments, while not deteriorating the cellular functionalities. On-demand disassembly at targeted lesion was then realized to facilitate CS module delivery and retrieval of the MA module. Furthermore, the feasibility of proposed system was validated in an in vivo rabbit bile duct. Therefore, this work presents a modular design–based strategy that enables uncompromised fabrication of multifunctional microrobots and stimulates their development for future cell-based therapy.
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Bioactive Materials
·
2021
·
IF 14.593
Longfa Kou,Xinyu Jiang,Yingying Tang,Xing Xia,Yingtao Li,Aimin Cai,Hailun Zheng,Hailin Zhang,Vadivel Ganapathy,Qing Yao,Ruijie Chen
Reprogramed cellular metabolism is one of the most significant hallmarks of cancer. All cancer cells exhibit increased demand for specific amino acids, and become dependent on either an exogenous supply or upregulated de novo synthesis. The resultant enhanced availability of amino acids supports the reprogramed metabolic pathways and fuels the malignant growth and metastasis of cancers by providing energy and critical metabolic intermediates, facilitating anabolism, and activating signaling networks related to cell proliferation and growth. Therefore, pharmacologic blockade of amino acid entry into cancer cells is likely to have a detrimental effect on cancer cell growth. Here we developed a nanoplatform ( [email protected] ) to therapeutically target two transporters, SLC6A14 (ATB 0,+ ) and SLC7A5 (LAT1), that are known to be essential for the sustenance of amino acid metabolism in most cancers. The [email protected] uses tryptophan to guide SLC6A14-targeted delivery of JPH203, a high-affinity inhibitor of SLC7A5. In the process, SLC6A14 is also down-regulated. We tested the ability of this strategy to synergize with the anticancer efficacy of lapatinib, an inhibitor of EGFR/HER1/HER2-assocated kinase. These studies show that blockade of amino acid entry amplifies the anticancer effect of lapatinib via interference with mTOR signaling, promotion of apoptosis, and suppression of cell proliferation and metastasis. This represents the first study to evaluate the impact of amino acid starvation on the anticancer efficacy of widely used kinase inhibitor.
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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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BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Ke Du,Yuting Liu,Lu Zhang,Lixia Peng,Wenjing Dong,Yajie Jiang,Mingming Niu,Yuanchao Sun,Chuanhong Wu,Yujuan Niu,Yonghe Ding
Because of its enhanced antitumor efficacy, lapatinib (LAP) is commonly used clinically in combination with the anthracycline drug doxorubicin (DOX) to treat metastatic breast cancer. While it is well recognized that this combination chemotherapy can lead to an increased risk of cardiotoxicity in adult women, its potential cardiotoxicity in the fetus during pregnancy remains understudied. Here, we aimed to examine the combination of LAP chemotherapy and DOX-induced cardiotoxicity in the fetus using a zebrafish embryonic system and investigate the underlying pathologic mechanisms. First, we examined the dose-dependent cardiotoxicity of combined LAP and DOX exposure in zebrafish embryos, which mostly manifested as pericardial edema, bradycardia, cardiac function decline and reduced survival. Second, we revealed that a significant increase in oxidative stress concurrent with activated MAPK signaling, as indicated by increased protein expression of phosphorylated p38 and Jnk, was a notable pathophysiological event after combined LAP and DOX exposure. Third, we showed that inhibiting MAPK signaling by pharmacological treatment with the p38MAPK inhibitor SB203580 or genetic ablation of the map2k6 gene could significantly alleviate combined LAP and DOX exposure-induced cardiotoxicity. Thus, we provided both pharmacologic and genetic evidence to suggest that inhibiting MAPK signaling could exert cardioprotective effects. These findings have implications for understanding the potential cardiotoxicity induced by LAP and DOX combinational chemotherapy in the fetus during pregnancy, which could be leveraged for the development of new therapeutic strategies.
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FREE RADICAL BIOLOGY AND MEDICINE
·
2025
·
IF 8.2
Ru Li,Yimei Ma,Anqi He,Yamin Pu,Xuanting Wan,Hongbao Sun,Ningyu Wang,Min Luo,Guan Wang,Yong Xia
The multi-kinase inhibitor sorafenib has shown potential to inhibit tumor cell growth and intra-tumoral angiogenesis by targeting several kinases, including VEGFR2 and RAF. Abnormal activation of the Ras/Raf/MAPK/ERK kinase cascade and the VEGF pathway is a common feature in breast cancer. However, the efficacy of sorafenib in breast cancer treatment remains limited. Recently, fasting has emerged as a promising non-pharmacological approach to modulate cancer metabolism and enhance the effectiveness of cancer therapies. In this study, we found that fasting significantly enhances the anti-cancer effects of sorafenib monotherapy and its combination with immunotherapy in breast cancer models without causing obvious side effects. This combined treatment effectively inhibits tumor cell proliferation and intra-tumoral angiogenesis. The fasting-induced reduction in peripheral blood glucose levels strongly correlated with enhanced sensitivity to sorafenib. Mechanistically, the combined treatment induced mitophagy, characterized by mitochondrial dysfunction and activation of the PINK1-Parkin pathway. Consequently, increased mitochondrial ROS levels promoted p53 expression, amplifying cell cycle arrest and apoptosis in breast cancer cells. Furthermore, fasting reduced lactate levels within the tumor, and the consequent glucose limitation synergized with sorafenib to activate AMPK, which in turn elevated PD-L1 expression in tumor cells, potentially enhancing their sensitivity to immunotherapy. In summary, our findings demonstrate that fasting and sorafenib, as a rational combination therapy, induce mitophagy, thereby enhancing sorafenib's efficacy in treating breast cancer through the ROS-driven p53 pathway. This study underscores the potential of fasting in breast cancer therapy and provides a foundation for optimizing the clinical application of sorafenib.
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