MICROCHEMICAL JOURNAL
·
2026
·
IF 5.1
Sai-Nan Qin,Yi-Xue Zhang,Yi-Jie Cao,Ting Wan,Yi-Yang Zhou,Shan-Shan Su,Yu-Qiong Guo,Jian-Jun Sun,Kalle Salminen
Cisplatin (DDP), as a broad-spectrum anticancer drug, requires dynamic monitoring of its blood concentration and intervention in its dosage administration to balance efficacy and safety due to significant individual differences in its metabolism, side effects, and resistance in different patients. However, rapid and robust methods for monitoring and quantifying DDP in complex biological fluids are still lacking. This work presents an electrochemical aptamer-based ( E -AB) sensor for rapid measurement of DDP concentration in blood. In which capture probe aptamers were designed constructed by visualizing and analyzing their binding pockets, followed by molecular docking and circular dichroism to screen the aptamer Apt25, which has a small binding energy and a large conformational change, for use in the construction of the sensor. In the presence of DDP, the aptamer undergoes a conformational change at the electrode interface, altering the electron transfer rate of the electroactive label to detect DDP concentration variations. After systematically using electrochemical techniques to optimize the sensor testing conditions, the sensor can directly analyze and detect DDP in urine and blood with a measurement range of 0.001–2 mM and a detection limit of 1 μM, which satisfies the needs of clinical testing. The spiked recoveries in different biological samples were 80.8–110% and 79–115.2%, respectively. In addition, the sensor has sufficient selectivity and stability, which is expected to enable real-time monitoring of DDP concentration for dosage adjustment and improvement of drug bioavailability at the clinical site.
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Soft Matter
·
2022
·Vol. 18
·期 16
·3157-3167
·
IF 4.046
Zhouxuan Xiang,Ting Liu,Huimin Wang,Genxin Chen,Xiongbin Zhu,Tonghui Hao,Jiabing Ran,Changying Yang
Developing customizable pH-responsiveness for supramolecular hydrogels is of great significance and has drawn tremendous attention. Through systematic simulation analysis, we formulated a simple supramolecular hydrogel (i.e., poly(AAm-co-NaSS)/BSA on the basis of electrostatic interaction between the sulfonate groups of poly(AAm-co-NaSS) and the protonated side groups of BSA, and proposed a novel pH-responsive mode for it: changing the internal electric charge composition of the hydrogel through pH-induced ionization/protonation transition of BSA, thereby regulating the structural stability/shrinkage/extension of the supramolecular network. On basis of this theory, the pH-responsiveness of the poly(AAm-co-NaSS)/BSA hydrogel, in principle, could be pre-designed by adjusting the initial BSA/NaSS ratio. In this regard, we fabricated a poly(AAm-co-NaSS)/BSA hydrogel prototype with a BSA/NaSS ratio of 1/57 and investigated its rheological/swelling/disassembling behavior under different pH conditions (1.7, 4.7, 7.7, 10.7, and 13.7). In addition, we also prepared two capecitabine-loaded poly(AAm-co-NaSS)/BSA hydrogel prototypes with BSA/NaSS ratios of 1/57 and 1/102 respectively at pH 4.0, and compared their drug release behavior in SGF and SIF. Finally, the experimental results fitted well with our theoretical expectations, which testified the rationality of our assumption. Thus, we believed that the poly(AAm-co-NaSS)/BSA supramolecular hydrogel could find diverse applications in the future.
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PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 13
·4019
·
IF 4.927
Hanwen Liu,Ying Liu,Ting Zhou,Penghui Zhou,Jianguo Li,Anping Deng
5-Fluorouracil (5-FU) is an effective anticancer drug widely used in the world. To improve therapy efficiency and reduce side effects, it is very important to frequently detect the concentration of 5-FU in blood samples of patients. In this work, a new type of lateral flow immunochromatographic assay (LFIA) based on surface-enhanced Raman scattering (SERS) for ultrasensitive and specific detection of 5-FU in blood samples was developed. Au@Ag/Au nanoparticles (NPs) employing Au particles as the core and Ag/Au alloy as the shell were synthesized, characterized and used as the substrate in SERS-LFIA due to their high SERS enhancement and biocompatibility. The immunoprobe was made in the form of AuMBA@Ag/Au-Ab in which mercaptobenzoic acid (MBA, a common Raman active reporter) was embedded in the core–shell layer and the monoclonal antibody (mAb) against 5-FU was immobilized on the surface. The performance of SERS-LFIA was similar to that in colloidal gold based-LFIA, and the entire assay time was within 20 min. According to the color intensity on the testing (T) lines of LFIA strips visualized by eyes, the contents of 5-FU in the samples could be qualitatively or semi-quantitatively identified. Furthermore, by measuring the characteristic Raman intensities of MBA on T lines, quantitative detection of 5-FU in the samples were achieved. The IC50and limit of detection (LOD) of the LFIA for 5-FU were found to be 20.9 pg mL−1and 4.4 pg mL−1, respectively. There was no cross-reactivity (CR) of the LFIA with nine relative compounds, and the CR with cytosine, tegafur and carmofur were less than 4.5%. The recoveries of 5-FU from spiked blood samples were in the range of 78.6~86.4% with the relative standard deviation (RSD) of 2.69~4.42%. Five blood samples containing 5-FU collected from the Cancer Hospital were measured by SERS-LFIA, and the results were confirmed by LC-MS/MS. It was proven that the proposed method was able to simply and rapidly detect 5-FU in blood samples with high sensitivity, specificity, accuracy and precision.Keywords:surface-enhanced Raman scattering (SERS);lateral flow immunochromatographic assay (LFIA);5-fluorouracil (5-FU);anticancer drug;blood samples
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高影响因子
TALANTA
·
2022
·
IF 6.556
Ting Zhou,Guangzhao He,Changjia Hu,Kang Wu,Ying Liu,Jianguo Li,Anping Deng
5-Fluorouracil (5-FU) is an effective anticancer drug widely used in cancer treatment. In this study, two 5-FU derivatives containing a spacer arm with the carboxylic group at the end were synthesized, which were linked to the carrier proteins to form 5-FU-protein conjugates used as the immunogens for the production of monoclonal antibody (mAb). Based on the produced mAb, the highly sensitive and specific enzyme-linked immunosorbent assay (ELISA) for 5-FU detection was established. The IC 50 and LOD values of the assay were found to be 19.5 ng mL −1 and 0.5 ng mL −1 , respectively. There was no cross-reactivity (CR) of the ELISA with cytosine , thymine and uracil , which avoided the interference from inherent pyrimidines. The CR values of the assay with three substitutes of 5-FU (tegafur, 5-fluoro-2′-deoxyuridine, carmofur) were within 9.7%–17.6%. The produced mAb was also applied in sample extraction. The immuno-affinity column capable specific capturing 5-FU was prepared by immobilizing the mAb on Sepharose-4B gel and filling into a SPE column. The recoveries of 5-FU in spiked samples measured by ELISA were 72.4%–90.7% with RSD of 3.6%–8.3%. Five blood samples collected from patients were extracted by immuno-affinity column, then measured by ELISA and confirmed by HPLC-MS/MS. There was a good correlation between HPLC-MS/MS and ELISA. It is demonstrated that the developed ELISA combined with immuno-affinity extraction can be a powerful alternative method for the detection of 5-FU in blood samples.
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高影响因子
Materials Chemistry Frontiers
·
2022
·Vol. 6
·期 19
·2859-2868
·
IF 8.683
Ming Liu,Ran Cen,Ji-Hong Lu,Tie-Hong Meng,Chun-Rong Li,Carl Redshaw,Timothy J. Prior,Zhu Tao,Xin Xiao
Fluorescent nitrogen and fluorine doped carbon dots (CDs) were prepared by a hydrothermal method using levofloxacin (LVFX) and cucurbit[6]uril (Q[6]) as the nitrogen and carbon sources, respectively. Decomposition of LVFX occurred at elevated temperature affording N,N′-desethylene levofloxacin hydrochloride (N,N′-DLH). The crystal structure of the resulting inclusion complex N,N′-DLH@Q[6]·[CdCl4]2(H3O)·9H2O was determined, where N,N′-DLH is protonated on each of the terminal nitrogens and the quinone functionality is a quinol which forms an intramolecular hydrogen bond to the carboxylic acid. The synthesized N,N′-DLH containing Q[6]-CDs emitted intense blue fluorescence with high photostability and exhibited stability at high ionic strength. In particular, the original rigid macrocyclic skeletons of these hosts were retained during the fabrication process, which helps in uniquely distinguishing them from other reported CDs. Meanwhile, the performance of the Q[6]-CDs was characterized using fluorescence and NMR spectroscopies. Subsequently, using the obtained Q[6]-CDs, an efficient sensing method for L-tryptophan (L-Trp) and capecitabine (CAP) has been developed based on macrocyclic host–guest chemistry. Under applicable conditions, the detection limits for L-Trp and CAP were calculated to be 5.13 × 10−8 M and 1.48 × 10−8 M, respectively.
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CHEMICAL ENGINEERING JOURNAL
·
2020
·
IF 10.652
Shaoyu Tang,Lei Xu,Xiaolong Yu,Shuona Chen,Huanyong Li,Ying Huang,Junfeng Niu
Degradation of capecitabine was conducted using electrochemical oxidation, UV/H 2 O 2 oxidation, and ozonation. Capecitabine was efficiently degraded by three advanced oxidation processes. The degradation rates of capecitabine achieved approximately 99.0% after 4 min of ozonation, 12 min of electrochemical oxidation, and 30 min of UV/H 2 O 2 oxidation. The mineralization rate obtained was merely 10.3% for ozonation at 60 min, compared to 91.7% for electrochemical oxidation and 55.3% for UV/H 2 O 2 oxidation. Capecitabine was degraded by oxidation, defluorination, hydrogenation, hydrolysis, ring and bond cleavage. Thus, multiple intermediates were generated during the degradation process, such as F - , formic acid, acetic acid, oxalic acid, and other intermediate metabolites with lager molecules. A total of eighteen metabolites, except for F - and carboxylic acids, were identified by QTOF-HRMS, where six of them could only be detected by the electrochemical oxidation process, two of them were by the UV/H 2 O 2 oxidation process, and one of them by the ozonation process. Electrochemical oxidation was the only process that could achieve over 90% removal of cytotoxicity and genotoxicity, and the metabolites were non-genotoxic after 60 min of reaction. The number of live cells decreased with the increasing reaction time in ozonation, demonstrating the higher toxicity of the intermediates in ozonation. Energy cost evaluation results suggested that the lowest energy consumption was achieved at 1.8 kWh/m 3 for 90% of capecitabine degradation with the O 3 dosage of 250 mg/h. Energy consumptions for 50% removal of cytotoxicity were 21.3 and 6.3 kWh/m 3 in electrochemical oxidation and UV/H 2 O 2 oxidation, respectively. The highest energy cost for 50% of genotoxicity removal was observed in electrochemical oxidation, while ozonation was identified as the most cost-effective process.
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Frontiers in Oncology
·
2023
·
IF 4.7
Zhu Yan,Ding Zhechun,Wang Yini,Wu Qing,Chen Dongmei,Wang Luanhong,Li Yuancheng,Yao Yao,Huang Jiman,Li Yun,Wang Xiaojing,Lin Yanchun,Guan Tian,Zeng Haoyu,Li Congzhu
Introduction: In cancer treatment, every minute counts. Due to the unpredictable behavior of cancer cells caused by continuous mutations, each cancer patient has a unique situation and may or may not respond to a specific drug or treatment. The process of finding an effective therapy can be time-consuming, but cancer patients do not have the luxury of time for trial and error. Therefore, a novel technology to fast generate a patient relevant organoid for the therapies selecting is urgently needed.Methods: Utilizing the new organoid technology by specially dissolving the mesenchyme in tumor tissues acquired from cancer patients, we realized the work of creating patient-specific organoids (PSO) within one day.Results: PSO properties reflect those of its respective original in vivo tumor tissue and can be utilized to perform various in vitro drug sensitivity tests to identify the most effective clinical treatment for patients. Additionally, PSO can aid in assessing the efficacy of immune cell therapies.Discussion: Organoid technology has advanced significantly in recent years. However, current cancer organoid methods involve creating 3D tumor tissue from 2D cancer cells or cell clusters, primarily for cancer research purposes aimed at investigating related molecular and cellular mechanisms of tumor development. These methods are research-driven, not tailored towards clinical applications, and cannot provide personalized information for individual patients. PSO filled the gap of clinic-driven and time-saving method for the personalized therapies selecting to the cancer patients.
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高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Yiren Yang,Pengyu Liu,Yue Jin,Huilin Zhu,Miao Wang,Xiaowen Jiang,Huiyuan Gao
Background Conventional chemotherapy medications are inadequate for managing the primary or acquired drug resistance, high toxicity, and adverse effects of colorectal cancer (CRC) treatment. Ursolic acid (UA) and Solasodine (Sol) are natural compounds found in a wide variety of traditional medicinal plants, as well as in many fruits and vegetables, such as Actinidia arguta (Sieb. & Zucc) Planch and Solanum nigrum L.. These compounds exhibit significant anti-tumor activity. Recent investigations have demonstrated that a combination strategy using natural products exhibits greater potential in CRC treatment compared to a single-drug strategy. Purpose This study aimed to elucidate the potential of UA-Sol synergy against CRC and to investigate the mechanism of action involved in inducing apoptosis and inhibiting metastasis through the AKT1/ERK1/2-GSK-3 β - β -catenin axis. Methods The optimal ratio of UA-Sol and its synergistic effects were explored using an MTT assay combined with the technique of Chou Talalay. The effects of UA-Sol on the apoptosis, autophagy, and metastasis of CRC cells were assessed using Annexin V-FITC/PI, TUNEL, Immunofluorescence, Wound healing, Transwell migration, and western blotting. The core mechanism of action of UA-Sol against CRC was investigated employing network pharmacology prediction combined with CETSA and plasmid transfection. Finally, in vivo validation was conducted using mouse xenograft tumor and lung metastasis models. Results The combination of UA and Sol synergistically inhibited CRC cell viability at a molar ratio of 6:24. UA-Sol induced the expression of pro-apoptotic and autophagy genes such as Bax/Bcl-2 and LC3, ultimately leading to apoptosis and autophagy in CRC cells in vitro . In addition, this combination inhibited MMP-9 and promoted the expression of the adhesion protein E-cadherin, thereby inhibiting CRC cell metastasis. Mechanistically, UA-Sol regulated the expression of a downstream protein GSK-3 β by targeting AKT1 and ERK1/2 inhibition. This induced a cross-talk between the MAPK cascade pathway and the PI3K/AKT pathway, thereby inhibiting the nuclear translocation of β -catenin and participating in the regulation of CRC cell processes. Conclusion UA-Sol inhibited the AKT1/ERK1/2-GSK-3 β - β -catenin axis to induce apoptosis, autophagy and anti-metastasis by targeting AKT1 and ERK1/2 inhibition. This dual-target drug combination strategy provides promising insights into the development of novel, safe, and efficient drugs for the treatment of CRC.
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高影响因子
Materials Today Communications
·
2024
·
IF 3.7
Chensi Zeng,Yanfang Gong,Chenxi Qi,Xianghua Zeng,Ni Tan
Capecitabine (CAP) is a kind of prodrug that can be metabolized into 5-fluorouracil (5-FU) in vivo, so it is usually classified as the antimetabolite fluoropyrimidine deoxynucleoside analog. In this paper, CAP, upconversion nanoparticles (UCNPs), 3,5-dicarboxy-4-methacrylate-based azobenzene (MAPDIA)/acrylic acid-functionalized gelatin, N,N′-methylene bisacrylamide (MBA), and ammonium persulfate (APS) were used as template, light trigger, bifunctional monomers, cross-linking agent and initiator, respectively. By using the free-radical polymerization and the molecular imprinting technique, the potential drug delivery nanocontainer CAP-MIP with the dual-responsive performance to pH/near infrared light (NIR) was successfully prepared. Furthermore, the characterization of CAP-MIP was also carried out by the modern instrumental analysis such as FTIR, XRD, TGA, BET and so on. The stimulus-responsive release experiment in vitro indicated the maximum cumulative release rate of CAP changed from 1.71 % to 89.54 % when the pH value in medium varied from 1.2 to 8.3, and the equilibrium release time point also greatly prolonged to 420 min from 40 min, respectively. When irradiated by 980 nm monochromatic NIR light in the same solution of pH 6.8, the maximum release rate of the sample could reach 96.21 % at 180 min, which respectively corresponded to the data of 41.84 % at 420 min under the condition of the absence of additional NIR light. In addition, CAP-MIP also had the excellent specific adsorption for CAP with the selectivity factor of 2.904 and the maximum CAP-loaded capacity of 7 mg•g −1 . The above information denoted the target material should be of some potential in drug delivery system application.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Shuliang Song,Xiao Zhang,Lei Cui,Yan Wang,Xiao Tian,Ke Wang,Kai Ji
Malignant tumors contribute significantly to human mortality. Chemotherapy is a commonly used treatment for tumors. However, due to the low selectivity of chemotherapeutic drugs, immune cells can be damaged during antitumor treatment, resulting in toxicity. Lipopolysaccharide (LPS) can stimulate immune cells to respond to foreign substances. Here, we found that 10 ng/mL LPS could induce tolerance to antitumor drugs in macrophages without altering the effect of the drugs on tumor cells. Differentially expressed genes (DEGs) were identified between cells before and after LPS administration using transcriptome sequencing and found to be mainly associated with ATP-binding cassette (ABC)-resistant transporters and glutathione S-transferase (GST). LPS was shown by qRT-PCR and western blotting to promote the expression of ABCC1, GSTT1, and GSTP1 by 38.3 %, 194.8 %, and 27.0 %. Furthermore, three inhibitors (inhibitors of GST, glutathione synthesis, and ABCC1) were used for further investigation, showing that these inhibitors reduced macrophage survival rates by 44.0 %, 52.3 %, and 43.3 %, while the intracellular adriamycin content increased by 28.9 %, 42.9 %, and 51.3 %, respectively. These findings suggest that the protective mechanism of LPS on macrophages is associated with increased GST activity, the consumption of glutathione, and increased expression of ABCC1 protein. Therefore, LPS has a potential role in enhancing immunity.
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高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Yuteng Tang,Yuanhang Xiang,Yu Yang,Yuyuan Zhang,Binqi Wei,Xiaojie Qin,Min Fang,Qiqin Wang,Xinchun Li,Fan Yang
The unmet on-site clinical diagnostics are increasingly demanding portable bioassays, but compromised by sensitivity and throughput. Herein, a nanostructured bubbles-enhanced fluorescence (nBEF) assay is reported by interfacing with smartphone imaging system to enable portable, ultrasensitive, and specific miRNA detection in parallel. In nBEF, the high-curvature bubbles allow physically enhancing optical propagation, chemically enhancing fluorescence, assembling more DNA probes, undergoing faster self-suspension and more efficient self-aggregation fluorescence enhancement relative to their smooth counterparts. By coupling with bubble-driven signal amplification by a plug-and-play DNA concatemer, and with a smartphone imaging system, this nBEF assay achieves a portable and ultrasensitive fluorescent assay of miRNA at the femtomolar level with one-base resolution in a single test, and is capable of monitoring drug-induced miRNA dynamic expression and accurate cancer diagnosis (AUC = 1) through profiling 40 plasma samples after RNA extraction. This assay further integrates an R-value analysis in RGB module with the smartphone to realize automated, on-site miRNA readout. Such a high-performance nBEF assay provides a low-cost, portable, and highly sensitive tool to enable accurate clinical diagnosis.
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高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Xinqi Qiu,Minhui Zhang,Yan Liu,Mingao Li,Quanzhou Wu,Jianfeng He
A novel water-compatible surface molecularly imprinted polymer microspheres (SMIMs) based on boronate affinity and hydrophilic coating were developed for the specific recognition and extraction of capecitabine (CAP). The boronic acid-functionalized polymer microspheres (BPMs) were first prepared as the carrier through dispersion polymerization using methyl methacrylate, ethylene glycol dimethacrylate, and 4-vinylphenylboronic acid as the polymerization monomers. Subsequently, the CAP template was immobilized onto the surface of the BPMs by virtue of boronate affinity. Finally, a thin and adherent imprinting layer was coated onto the surface of the BPMs via in-water self-polymerization of dopamine (DA) and polyethyleneimine (PEI). The resulting SMIMs exhibited strong hydrophilicity, high adsorption capacity (151.52 μmol/g) and a great imprinting factor (5.99) for CAP in aqueous media. The adsorption behavior of CAP onto the SMIMs was in good agreement with the Langmuir model and the pseudo-second-order equation. Selective adsorption indicated that the SMIMs exhibited a higher specific recognition for CAP compared to other structural analogs. In addition, the SMIMs showed excellent reproducibility and reusability, and could be utilized as an adsorbent in solid-phase extraction (SPE) for the selective pre-concentration, purification, and detection of trace amounts of CAP in spiked urine samples in combination with HPLC. The elution recovery of CAP for the various spiked levels ranged from 91.7 % to 104.9 %, with a relative standard deviation (RSD) of less than 5.8 % (n = 3).
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