JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2024
·
IF 3.1
Mengru Bai,Qian Shen,Yong Wu,Zhiyuan Ma,Yuqing Wang,Mingyang Chen,Dan Liu,Lin Zhou
Methotrexate (MTX) is commonly prescribed as the initial treatment for gestational trophoblastic neoplasia (GTN), but MTX monotherapy may not be effective for high-risk GTN and choriocarcinoma. The cellular uptake of MTX is essential for its pharmacological activity. Thus, our study aimed to investigate the cellular pharmacokinetics and transport mechanisms of MTX in choriocarcinoma cells. For the quantification of MTX concentrations in cellular matrix, a liquid chromatography-tandem mass spectrometry method was created and confirmed initially. MTX accumulation in BeWo, JEG-3, and JAR cells was minimal. Additionally, the mRNA levels of folate receptor α (FRα) and breast cancer resistance protein (BCRP) were relatively high in the three choriocarcinoma cell lines, whereas proton-coupled folate transporter (PCFT), reduced folate carrier (RFC), and organic anion transporter (OAT) 4 were low. Furthermore, the expression of other transporters was either very low or undetectable. Notably, the application of inhibitors and small interfering RNAs (siRNAs) targeting FRα, RFC, and PCFT led to a notable decrease in the accumulation of MTX in BeWo cells. Conversely, the co-administration of multidrug resistance protein 1 (MDR1) and BCRP inhibitors increased MTX accumulation. In addition, inhibitors of OATs and organic-anion transporting polypeptides (OATPs) reduced MTX accumulation, while peptide transporter inhibitors had no effect. Results from siRNA knockdown experiments and transporter overexpression cell models indicated that MTX was not a substrate of nucleoside transporters. In conclusion, the results indicate that FRα and multiple transporters such as PCFT, RFC, OAT4, and OATPs are likely involved in the uptake of MTX, whereas MDR1 and BCRP are implicated in the efflux of MTX from choriocarcinoma cells. These results have implications for predicting transporter-mediated drug interactions and offer potential directions for further research on enhancing MTX sensitivity.
研究领域:
药理学
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肿瘤学
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细胞生物学
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分析化学
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产品关联
DOI
PubMed
高影响因子
ELECTROCHEMISTRY COMMUNICATIONS
·
2012
·
IF 4.859
Yuehong Pang,Zhaoqiang Ge,Yong Liu,Xiaofang Shen
Covalently conjugating folate on Au surface was achieved via click chemistry, copper (I)-catalyzed azide-alkyne cycloaddition reaction. Human leukemia K562 cells were used as a model system to investigate capturing cancer cells by folate-targeted electrode. Scanning optical microscopy and electrochemical method were used to monitor the capture of K562 cells on folate-clicked electrode.
研究领域:
生物化学
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医学工程
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分子生物学
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产品关联
DOI
高影响因子
JOURNAL OF FLUORESCENCE
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2021
·Vol. 31
·期 2
·339-348
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IF 2.217
Lv Rongyao,Li Genrong,Lu Shuting,Wang Ting
Carbon dots are nano-sized photoluminescence materials which have good biocompatibility and low cytotoxicity, while the previously synthesized carbon dots lack tumor targeting capability and therapy function so that it cannot achieve the purpose of diagnosis and treatment. Herein, a new kind of multi-functional carbon dots (GFCDs) is promising to be applied in tumor cells imaging and clinical targeted therapy. Gallic acid (GA) was used as the carbon resource and antitumor active molecule, folic acid (FA) was used as the nitrogen resource and tumor targeting molecule, and citric acid monohydrate (CA) was used as the auxiliary carbon source. Multi-functional GACDs were synthesized by a simple one-step microwave-assisted procedure and analyzed with UV − vis spectrophotometer, fourier transform infrared spectrometer, transmission electron microscopy and X-ray photoelectron spectrometer. Results show that the diameter of GFCDs is about 3 nm. And GFCDs are pale-yellow under natural light which turn blue under 360 nm UV lamp. Besides ester bond is the connecting mode between functional molecules. In addition, the results of in vitro cell imaging experiments and in vivo antitumor experiments demonstrate the targeting imaging and antitumor abilities towards Hela cells. Graphical abstract
The synthesis route and properties of GFCDs.
研究领域:
生物医学工程
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2017
·
IF 4.164
Xin Ji,Huilong Guo,Qiao Tang,Dong Ma,Wei Xue
Antitumor efficacy of methotrexate (MTX) is seriously limited due to its poor water solubility, nonspecific tumor distribution and low bioavailability. To overcome these obstacles, polyspermine (PSP) conjugated with MTX and folic acid (FA) as a novel targeted prodrug was designed and has been successfully synthesized using the amidation reaction. The strong hydrophilic properties of PSP made MTX well dispersed in water and the cellular uptake study indicated that the presence of FA enhanced uptake of the FA-PSP-MTX in folate receptor (FR) over-expressing human nasopharyngeal carcinoma HNE-1 cells. 1 H NMR spectra and UV–Vis spectral analysis were carried out to confirm the MTX and FA content in FA-PSP-MTX, respectively. In CCK-8 assay and apoptosis analysis, the prodrug showed significantly enhanced anticancer efficacy than free MTX in HNE-1 cells. These results suggested that the prodrug has the potential for targeted delivery of MTX into cancer cells to improve its anti-tumor efficacy.
研究领域:
药理学
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肿瘤学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Chemistry Frontiers
·
2018
·Vol. 2
·期 8
·1529-1538
·
IF 0
Lijing Niu,Feiyan Zhu,Bowen Li,Lingling Zhao,Hongze Liang,Yinghua Yan,Hui Tan
A folate-conjugated and pH-sensitive polymeric micellar system for the co-delivery of DOX and PTX was studied. A doxorubicin conjugated prodrug was synthesized via Schiff's base reaction. Subsequently, folate was grafted onto the prodrug and PTX was encapsulated. Sustained drug release of both DOX and PTX from the polymeric micelles was observed and the release rate could be accelerated by decreasing the media pH. A cellular uptake assay revealed that the polymeric micelles were internalized in the cytoplasm via endocytosis by SW1353 cells, and the cellular uptake was enhanced for the folate-conjugated micelles due to an active FR-mediated endocytosis pathway, showing stronger red fluorescence compared to that of non-folate micelles. The in vitro anticancer efficiency of the polymeric micellar system was evaluated using a cytotoxicity assay by incubating different drug formulations with the SW1353 cells. Both free drugs and micellar formulations displayed inhibition of cell growth at different levels, while the folate-conjugated dual-drug loaded polymeric micelles (Folate–Oxd–DOX/PTX) displayed a much lower IC50 value than other drug formulations, indicating a desirable in vitro anticancer efficiency due to the synergistic effect of co-delivery and active targeting. Thus, the polymeric micellar system is a promising platform for targeted cancer chemotherapy.
研究领域:
药剂学
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肿瘤学
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生物材料
✓ 已验证
产品关联
DOI
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2018
·Vol. 19
·期 10
·3132
·
IF 3.687
Liang Li,Na Liang,Danfeng Wang,Pengfei Yan,Yoshiaki Kawashima,Fude Cui,Shaoping Sun
The present investigation aimed to develop a tumor-targeting drug delivery system for paclitaxel (PTX). The hydrophobic deoxycholic acid (DA) and active targeting ligand folic acid (FA) were used to modify water-soluble chitosan (CS). As an amphiphilic polymer, the conjugate FA-CS-DA was synthesized and characterized by Proton nuclear magnetic resonance (1H-NMR) and Fourier-transform infrared spectroscopy (FTIR) analysis. The degree of substitutions of DA and FA were calculated as 15.8% and 8.0%, respectively. In aqueous medium, the conjugate could self-assemble into micelles with the critical micelle concentration of 6.6 × 10−3mg/mL. Under a transmission electron microscope (TEM), the PTX-loaded micelles exhibited a spherical shape. The particle size determined by dynamic light scattering was 126 nm, and the zeta potential was +19.3 mV. The drug loading efficiency and entrapment efficiency were 9.1% and 81.2%, respectively. X-Ray Diffraction (XRD) analysis showed that the PTX was encapsulated in the micelles in a molecular or amorphous state. In vitro and in vivo antitumor evaluations demonstrated the excellent antitumor activity of PTX-loaded micelles. It was suggested that FA-CS-DA was a safe and effective carrier for the intravenous delivery of paclitaxel.Keywords:chitosan;deoxycholic acid;folic acid;amphiphilic polymer;micelles;paclitaxel
研究领域:
药剂学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NANO
·
2020
·
IF 1.566
Yujiao Tu,Xuemei Chen,Yingying Xiang,Xiaotian Yuan,Kunhao Qin,Yunlin Wei,Zhiwei Xu,Qi Zhang,Xiuling Ji
Highly blue fluorescence carbon dots (CDs-MCM) were successfully prepared via a simple hydrothermal method with citric acid and ethylene diamine tetraacetic acid doped mesoporous silica MCM-41. The CDs-MCM exhibited uniform particle size and possessed good excitation-dependent characteristic. It showed highly selectivity and sensitivity in detection of Cr(VI), folic acid and good linear ranges of 0–37.5 μ M ( R 2 = 0 . 9 9 0 3 ) and 0–50 μ M ( R 2 = 0 . 9 9 4 9 ). The low detection limits were 79.31 nM and 118.73 nM for Cr(VI) and folic acid, respectively. It revealed that inner filter effect dominated in Cr(VI) quenching of the CDs-MCM fluorescent, while that of folic acid belonged to static quenching. The CDs-MCM were successfully used to detect the Cr(Vl) and folic acid in water and vegetable samples with satisfactory results. It provided new insight into environmental Cr(VI) and folic acid detection.
研究领域:
环境科学
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分析化学
✓ 已验证
产品关联
DOI
高影响因子
DRUG METABOLISM AND DISPOSITION
·
2024
·Vol. 52
·期 11
·1332-1344
·
IF 4.4
Yuqing Wang,Jun Luo,Mengru Bai,Zhiyuan Ma,Ying Xu,Dan Liu,Huidi Jiang,Shenglin Ma,Shirong Zhang
Antifolates are important for chemotherapy in non–small cell lung cancer (NSCLC). They mainly rely on reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT) to enter cells. PCFT is supposed to be the dominant transporter of the two in tumors, as it operates optimally at acidic pH and has limited transport activity at physiological pH, whereas RFC operates optimally at neutral pH. In this study, we found RFC showed a slightly pH-dependent uptake of antifolates, with similar affinity values at pH 7.4 and 6.5. PCFT showed a highly pH-dependent uptake of antifolates, with an optimum pH of 6.0 for pemetrexed and 5.5 for methotrexate. The Michaelis-Menten constant (Km) value of PCFT for pemetrexed at pH 7.4 was more than 10 times higher than that at pH 6.5. Interestingly, we found that antifolate accumulations mediated by PCFT at acidic pH were significantly affected by the efflux transporter, breast cancer resistance protein (BCRP). The highest pemetrexed concentration was observed at pH 7.0–7.4 after a 60-minute accumulation in PCFT-expressing cells, which was further evidenced by the cytotoxicity of pemetrexed, with the IC50 value of pemetrexed at pH 7.4 being one-third of that at pH 6.5. In addition, the in vivo study indicated that increasing PCFT and RFC expression significantly enhanced the antitumor efficacy of pemetrexed despite the high expression of BCRP. These results suggest that both RFC and PCFT are important for antifolates accumulation in NSCLC, although there is an acidic microenvironment and high BCRP expression in tumors.
研究领域:
肿瘤学
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药理学
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分子生物学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2025
·
IF 6
Zhou Yang,Lingling Dai,Fangfei Liu,Kun Jia,Zhiyuan Ren,Yanmei Yang,Qingmeng Zhang,Weifeng Li,Ming Chen
Background Folate is an essential nutrient, but its bioavailability varies greatly depending on the molecular form present in food. The intake of forms that are not readily absorbed by the human body may lead to insufficient folate levels, particularly during pregnancy, thereby increasing the risk of birth defects. As a result, it is essential to develop a highly sensitive and accurate method capable of distinguishing between the two most common natural folates, 5-methyltetrahydrofolate (5-MTHF) and 5-formyltetrahydrofolate (5-FTHF), to ensure proper folate intake and health outcomes. Results In this study, a photochemical method was employed to load gold nanoparticles (Au NPs) onto carbon nanotubes (CNTs), successfully synthesizing CNTs@Au NPs nanocomposites that exhibit excellent thermal stability and robust surface-enhanced Raman scattering (SERS) activity. These nanocomposites, capable of maintaining structural integrity at temperatures as high as 400 °C, serve as highly effective substrates for in situ high-temperature SERS detection. Using this reliable high-temperature-assisted SERS approach, the structural changes of both folates at elevated temperatures were effectively monitored, enabling clear molecular fingerprinting and distinct differentiation between the two natural folates. Moreover, the CNTs@Au NPs demonstrate exceptional sensitivity, achieving a detection limit as low as 10 -8 M for both 5-MTHF and 5-FTHF, enabling accurate quantification of mixed folate samples and demonstrating reliable performance in real sample analysis. Significance The CNTs@Au NPs with in situ high-temperature SERS capabilities show great potential for various analytical applications. In particular, they provide an effective method for monitoring the quality of folate in dietary supplements and fortified foods, thus contributing significantly to the safety and quality assurance of folate products in the market.
研究领域:
分析化学
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纳米材料
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食品安全
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光谱学
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营养科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF POWER SOURCES
·
2025
·
IF 7.9
Mingliang Li,Lu Tian,Xinning Huang,Jinxiao Dou,Jianglong Yu,Xingxing Chen
Aqueous zinc-ion batteries (AZIBs) are recognized as one of the most promising battery technologies, but dendrite growth and persistent parasitic reactions at the Zn anode hinder their practical use. This study employs cost-effective and source-abundant folic acid (FA) as a multifunctional electrolyte additive, which is self-assembled at the Zn anode, forming an effective layer improving the reversibility and stability of the zinc anode/electrolyte interface. In-situ Raman reveals the electrostatic shielding effect of the layer against SO 4 2− anions. In-situ scanning vibrating electrode technique (SVET) further verifies the superior inhibitory effect of the interface layer on Zn anode corrosion. Practically, Zn//Zn symmetric battery filled with ZnSO 4 /0.1 FA electrolyte achieves a prominent cycling stability of 9500 h at 0.2 mA cm −2 and 0.2 mAh cm −2 , and the constructed Zn//Cu half battery exhibits a high reversibility (99.69 %) after 1045 cycles. Strikingly, Zn//MnO 2 full battery also demonstrates outstanding charge/discharge durability for at least 900 cycles with a high reversibility of >99.94 % at 5 C. This study provides a novel paradigm for the development of environmentally benign and cost-efficient electrolyte, pivotal in realizing exceptionally reversible AZIBs.
研究领域:
材料科学
·
电化学
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL RESEARCH IN CHINESE UNIVERSITIES
·
2018
·Vol. 34
·期 2
·203-211
·
IF 1.248
Song Shengmei,Li Minglu,Gong Xiaojuan,Han Hui,Zhou Yehong,Wang Li,Shuang Shaomin,Dong Chuan
In the paper, folic acid(FA)-mediated and β -cyclodextrin( β -CD) derivatives functionalized magnetic Fe 3 O 4 nanoparticles(MNPs) were successfully prepared as drug carriers for the targeted delivery and controlled release of water-insoluble anticancer drug. FA-sulfobutyl ether- β -CD-MNPs(FA-SBE- β -CD-MNPs), FA-hydroxypropyl- β -CD-MNPs(FA-HP- β -CD-MNPs) and FA-carboxymethyl- β -CD-MNPs(FA-CM- β -CD-MNPs) were fabricated, and the loading efficiency and relative entrapment rate of curcumin are 12.04 mg/g, 95.56% for FA-SBE- β -CD-MNPs, 9.6 mg/g, 81.63% for FA-HP- β -CD-MNPs and 7.88 mg/g, 85.28% for FA-CM- β -CD-MNPs, respectively. Meanwhile, at pH=5.0, the optimal release rate of curcumin is about 46.07% for FA-SBE- β -CD-MNPs in 5 h. Cellular uptake indicates that curcumin can be selectively transported to targeting site and released from the internalized carriers. The in vitro cytotoxicity reveals that non-toxic FA-SBE- β -CD-MNPs have excellent biocompatibility on HepG2 cells in the tested concentrations. Therefore, FA-SBE- β -CD-MNPs could provide a promising platform for the targeting delivery of water insoluble anti-cancer drugs for different treatment needs of cancer therapy.
研究领域:
药剂学
·
生物医学工程
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2021
·Vol. 45
·期 13
·5949-5957
·
IF 3.591
Xuexia Liu,Shuaihui Li,Limin Liu,Zhijun Wang
The development of active and stable carbon nanomaterials as electrocatalysts for the oxygen reduction reaction (ORR) remains a significant challenge. Herein, we report a one-step pyrolysis process to design hierarchical micro/mesoporous N-doped carbon (m-NC) materials using low-cost folic acid precursors. The optimal m-NC material carbonized at 750 °C (m-NC-750) displays a splendid ORR electrocatalytic activity and perfect stability in an alkaline medium (0.1 mol L−1 KOH). Notably, the current density of m-NC-750 can reach 4.35 mA cm−2 at 0.85 V, which surpasses that of commercial Pt/C (20 wt%). The higher electrocatalytic activity and activation of oxygen is due to the porous structures facilitating ion diffusion and the graphitic N dopant providing more active sites. In addition, the graphite N dopant of the m-NC material possesses the lowest energy barrier of reactions based on density functional theory (DFT) calculations, which effectively boosts the ORR of the as-prepared materials. This simple and economical method provides a facile way of designing high-performance carbon electrocatalysts for the ORR.
研究领域:
材料科学
·
电化学
·
催化材料
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）