JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2022
·
IF 3.571
Shenjia Huang,Linsheng Liu,Xiaoxue Liu,Lin Song,Chenrong Huang,Liyan Miao
In this study, a sensitive and rapid ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for the simultaneous analysis of cytarabine (ara-C), cytarabine monophosphate (ara-CMP), cytarabine diphosphate (ara-CDP) and cytarabine triphosphate (ara-CTP) in the cytosol and nucleus. The separation of analytes and endogenous interferents was achieved in 8 min on a hypercarb column (2.1 mm × 100 mm, 3 µm) by using a gradient elution with 95% acetonitrile and aqueous 5 mM hexylamine with 0.4% (v/v) diethylamine adjusted to pH 10. The analytes were detected with both negative and positive electrospray ionization in multiple reaction monitoring (MRM) mode. The calibration curve demonstrated good linearity ranging from 5 to 750 nM for ara-C, 50–7500 nM for ara-CMP, 20–3000 nM for ara-CDP and 1–150 nM for ara-CTP in the cytosol. In the nucleus, good linearity was achieved over a concentration range of 1–100 nM for ara-C, 5–500 nM for ara-CMP, 2.5–250 nM for ara-CDP and 0.5–50 nM for ara-CTP. Intra- and interbatch accuracies and precisions met the standards of validation. The matrix effect, recovery and stability were also within acceptable ranges. After incubation with 10 μM ara-C for 3 h, the levels of ara-C, ara-CMP, ara-CDP and ara-CTP in the cytosol and nucleus of HL-60 cells and HL-60/ara-C cells were determined. Most of the metabolites were found within the quantitation range. The results showed that the nuclear ara-CTP level was significantly different than the intracellular ara-CTP level between HL-60 and HL-60/ara-C cells.
研究领域:
药理学
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分析化学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-21
·
IF 10.435
Fei Weidong,Zhao Yunchun,Wu Xiaodong,Sun Dongli,Yao Yao,Wang Fengmei,Zhang Meng,Li Chaoqun,Qin Jiale,Zheng Caihong
Gestational trophoblastic tumors seriously endanger child productive needs and the health of women in childbearing age. Nanodrug-based therapy mediated by transporters provides a novel strategy for the treatment of trophoblastic tumors. Focusing on the overexpression of human equilibrative nucleoside transporter 1 (ENT1) on the membrane of choriocarcinoma cells (JEG-3), cytarabine (Cy, a substrate of ENT1)-grafted liposomes (Cy-Lipo) were introduced for the targeted delivery of methotrexate (Cy-Lipo@MTX) for choriocarcinoma therapy in this study. ENT1 has a high affinity for Cy-Lipo and can mediate the endocytosis of the designed nanovehicles into JEG-3 cells. The ENT1 protein maintains its transportation function through circulation and regeneration during endocytosis. Therefore, Cy-Lipo-based formulations showed high tumor accumulation and retention in biodistribution studies. More importantly, the designed DSPE-PEG2k-Cy conjugation exhibited a synergistic therapeutic effect on choriocarcinoma. Finally, Cy-Lipo@MTX exerted an extremely powerful anti-choriocarcinoma effect with fewer side effects. This study suggests that the overexpressed ENT1 on choriocarcinoma cells holds great potential as a high-efficiency target for the rational design of active targeting nanotherapeutics.Graphic abstract
研究领域:
药剂学
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肿瘤学
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分子生物学
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2018
·
IF 6.042
Mengzhe Guo,Liyan Zhang,Yan Du,Wencheng Du,Dantong Liu,Cheng Guo,Yuanjiang Pan,Daoquan Tang
5-(Hydroxymethyl)-2′-deoxycytidine (5-hmdC), 5-(formyl)-2′-deoxycytidine (5-fodC), and 5-(carboxyl)-2′-deoxycytidine (5-cadC) are crucial intermediate products of the DNA demethylation pathway, which can also act as potential biomarkers reflecting the diagnosis and prognosis in multiple tumors. Detecting 5-hmdC, 5-fodC, and 5-cadC in human urine has various advantages including readily available samples and being noninvasive to patients. However, few works have reported the detection of 5-fodC and 5-cadC due to their trace amounts. Here we developed a novel magnetic hyper-cross-linked microporous polymer (HMP) material based on polyionic liquid (PIL) for the enrichment of 5-hmdC, 5-fodC, and 5-cadC. These magnetic PIL-HMP materials provided specific enrichment superiority for three modified cytidines. After enrichment, the signal intensity of 5-hmdC, 5-fodC, and 5-cadC increased 10–75-fold with lower limits of quantitation (LLOQ) of 0.049, 0.781, and 0.781 ng/mL, respectively. The recoveries were approximately 86.5–95.2% for 5-hmdC, 95.2–107.8% for 5-fodC, and 99.4–102.4% for 5-cadC under the relative standard deviation (RSD) of 0.2–10.3%. Finally, we successfully applied magnetic PIL-HMP materials coupled with high-performance liquid chromatography–electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) in enrichment and quantitative determination of 5-hmdC, 5-fodC, and 5-cadC in human urine of 10 breast cancer patients and 10 healthy people. We found that the level of 5-hmdC decreased in breast cancer patients (p < 0.05), while the levels of 5-fodC and 5-cadC increased (p < 0.05, p < 0.01). Our results demonstrated that the levels of metabolic 5-hmdC, 5-fodC, and 5-cadC in human urine are closely related to breast cancer, which could contribute to the clinical diagnosis and investigation of breast cancer and its occurrence and development mechanisms.
研究领域:
医学
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分析化学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2017
·
IF 3.671
Jinsong Zhang,Youzhi Zhou,Ke Liu,Jianlin Chu,Yewei Zhang,Bingfang He
A novel nucleoside 2′-deoxyribosyltransferase ( Lh NDT) from Lactobacillus hilgardii ZJS01 was cloned and expressed in Escherichia coli BL21 (DE3). The amino acid sequence of Lh NDT displayed the highest identity of 26% to other reported NDTs. Lh NDT was a monomer as revealed by gel filtration chromatography with or without addition of Ca 2+ in elution buffer. This enzyme showed a high activity and stability over a broad pH range and was sensitive to temperature. With the addition of 15 mM Ca 2+ , the thermostability of Lh NDT was greatly promoted by 63 times and 46 times at 30 °C and 35 °C, respectively. With the use of 2′-deoxyuridine as sugar donor at an economic molar ratio of 1:1, 5-aza-2′-deoxycytidine (46%) and 5-fluoro-2′- deoxycytidine (58%) were efficiently synthesized from 5-azacytosine and 5-fluorocytosine, respectively, by Lh NDT for 2 h.
研究领域:
酶学
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生物技术
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioengineering
·
2024
·Vol. 3
·期 2
·151-159
·
IF 0
Ziye Zhao,Ning Nie,Xinwei Li,Ye Shi,Xudong Liu,Yifei Zhang
Nucleotides, such as uridine 5′-monophosphate (5′-UMP) and cytidine 5′-monophosphate (5′-CMP), are heavily demanded as food additives, dietary supplements, and medicinal intermediates. Although enzymatic phosphorylation is an effective approach to producing these nucleosides, its practical application is challenging due to the need for the expensive enzymes and coenzyme guanosine-5′-triphosphate (GTP). Here we prepared biocompatible calcium-based nanoflowers incorporated with cascade enzymes, uridine-cytidine kinase (UCK) and acetate kinase (ACK), for the production of nucleotides. The spatial distribution of these enzymes was optimized to maximize their catalytic performances. The most active nanoflowers (Ca 3 (PO 4 ) 2 & ACK)& UCK that display the rate-limiting enzyme UCK on the outer layer were used in a packed-bed reactor for continuous synthesis of 5′-UMP and 5′-CMP. The catalytic performance of the catalyst retained over 80% within 10 h, showing good operational stability.
研究领域:
生物催化
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纳米技术
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酶工程
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生物化学
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食品科学
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药物化学
✓ 已验证
DOI
JOURNAL OF ELECTROANALYTICAL CHEMISTRY
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2018
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IF 3.235
Jing Bao,Xintong Geng,Changjun Hou,Yanan Zhao,Danqun Huo,You Wang,Zhaonan Wang,Yan Zeng,Mei Yang,Huanbao Fa
Many studies have confirmed that DNA methylation is highly correlated with the occurrence and development of various diseases including cancers. In this work, we developed a simple, sensitive, selective, and universal electrochemical biosensor for detection of DNA methylation and assay of DNA methyltransferase (MTase) activity using M.SssI MTase as an example. The thiolated single-stranded DNA S1 was self-assembled on the surface of gold nanoparticles deposition modified glassy carbon electrode via Au S bonding, then hybridization between the DNA S1 and its complementary DNA S2 formed a double-stranded target sequence for both M.SssI MTase and restriction endonuclease Hpa II. HpaII could not cleave the target sequence after it was methylated by M.SssI MTase, while the sequence without methylation could be cleaved. Here, we used methylene blue (MB) as electrochemical indicator. The electrochemical signal of MB increased linearly with increasing M.SssI MTase concentration from 0.5 to 25 U/mL and from 25 to 400 U/mL with a detection limit of 0.04 U/mL. Moreover, screening of M.SssI MTase inhibitors 5-azacytidine (5-Aza) and 5-Aza-2′-deoxycytidine (5-Aza-dC) were successfully investigated using the fabricated electrochemical biosensor and showed that the two classic drugs could both inhibit the M.SssI MTase activity with the IC 50 of 2.8 μM and 0.37 μM, respectively, indicating potential application in discovery of new anticancer drugs.
研究领域:
生物化学
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分子生物学
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分析化学
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癌症研究
✓ 已验证
产品关联
DOI
高影响因子
Journal of Saudi Chemical Society
·
2021
·
IF 3.932
Lefeng Liu,Zhiguo Xu,Yang Liu,Zheng-Zhi Yin,Yanshan Sheng,Chengqiang Ding,Yong Kong
Cytarabine (Cyt) encapsulated calcium carbonate (CaCO 3 ) nanospheres were facilely synthesized through a simple co-precipitation method, and the Cyt encapsulated CaCO 3 nanospheres (CaCO 3 /Cyt) were modified by polyacrylic acid (PAA) hydrogels through in situ polymerization of acrylic acid (AA) monomer on the surface of the CaCO 3 /Cyt. Successful preparation of the Cyt loaded CaCO 3 /PAA hydrogels were confirmed by the characterization of SEM, TEM and FT-IR. Premature release of Cyt in acidic medium (pH = 1.2) could be effectively circumvented by the introduction of the PAA hydrogels. More importantly, pH-responsive delivery of Cyt from the as-prepared CaCO 3 /PAA hydrogels could be achieved due to the pH-sensitivity of the PAA. Although the highest swelling ratio of PAA was obtained at pH 7.3 (27.7), the highest cumulative release of Cyt from the carrier was achieved at pH 5.3 (86.75%), which might be attributed to the high stability of CaCO 3 at pH 7.3. That is to say, the highest cumulative release of Cyt at pH 5.3 was a compromise by considering the relatively high swelling ratio of PAA and the relatively low stability of CaCO 3 .
研究领域:
材料科学
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药学
✓ 已验证
产品关联
DOI
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Yong Hou,Tonghe Liu,Zhonghao Sun,Xudong Xu,Zhaocui Sun,Zongyang Li,Jianzhou Liu,Sichao Tian,Yihang Li,Nailiang Zhu,Haitao Liu,Guoxu Ma
Pancreatic cancer is one of the most devastating solid tumors and lacks ideal therapeutic options. The efficiency of using classic chemotherapeutic agents like gemcitabine (GEM) solely has been limited immensely owing to severe resistance and systemic toxicity, thus necessitating alternative multi-pronged strategies. Multicomponent supramolecular co-assembly leveraging natural small molecules (NSMs) cannot only produce carrier-free hydrogel materials having superior mechanical properties for convenient administration, but also achieve optimal synergies in combinational drugs therapy. Herein, a natural structural analog of GEM with favorable pro-apoptotic effect, adenosine (Ado), was found firstly to self-assemble spontaneously into a hydrogel (Ado-gel). Sequentially, we constructed a novel two-component hydrogel (DA-gel) via co-assembling Ado with another NSM evidenced here as new autophagy inhibitor, gentisic acid (2,5-dihydroxybenzoic acid, DHB). Addition of DHB had reinforced the thermal-responsiveness and viscoelasticity evidently in DA-gel, which ascribed to the heightened intermolecular hydrogen bonding and π-π stacking interactions. Together with its good injectability and biosafety, the local injection can be conducted smoothly so as to improve the compliableness of patients in clinical settings. More intriguingly, DA-gel was proven to exhibit the best anti-tumor efficiency in pancreatic carcinoma comparing with corresponding single-component and mixture in vitro and vivo , possibly due to its unique supramolecular structure amplifying two-component synergistic effects on inhibition of autophagy and mitochondrial injury, thus lead to more obvious apoptosis. Overall, the presented co-assembling strategy exhibits admirable synergistic effects, thereby may provide a new perspective for functional application of multiple NSMs and a promising alternative to current chemotherapy for the treatment of pancreatic cancer.
研究领域:
肿瘤学
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药剂学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2014
·
IF 4.287
Faheem Muhammad,Jianyun Zhao,Nan Wang,Mingyi Guo,Aifei Wang,Liang Chen,Yingjie Guo,Qin Li,Guangshan Zhu
Simultaneous delivery of multiple therapeutic agents is of great importance for effective chemotherapy due of its well-known drug synergism and suppression to chemoresistance. We report a new theranostic nanoformulation to shuttle multiple chemotherapeutic agents for successfully exterminating cancer cells. This strategy is based on the fabrication of magnetite doped mesoporous silica nanoparticles (MSNs) in which both internal porous and external surface of MSN are respectively exploited to load two different kinds of cytotoxic cargoes. Notably, an exceptionally high quantity (29%) of poorly hydrophobic drug camptothecin (CPT) is loaded into the nanopores of MSNs; however, in previous reports less than 1% loading efficiency is reported. Following CPT loading in the pores of MSNs, another unconventional but FDA approved arsenic trioxide (ATO) is conjugated onto the surface of nanocomposite via exploiting the thiophilic nature of ATO. Cell inhibition performance of dual drug nanoformulation is significantly higher than single drug formulation, possibly due to additional or synergistic effect, as low as 3 μg/ml of double drug nanocarrier were found effective to exterminate cancer cells. Besides drug delivery, the presence of superparamagnetic magnetite nanocrystals additionally empowers this system to be used as a contrast agent in magnetic resonance (MR) imaging for either monitoring diseased tissues or feedback of chemotherapy. We anticipate that the integration of combination therapy with nanotechnology coupled with versatile magnetic manipulation feature may prove a significant step forward toward the development of effective theranostic agents.
研究领域:
肿瘤学
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纳米医学
·
药物递送
✓ 已验证
DOI
PubMed
高影响因子
CHINESE JOURNAL OF CHEMICAL ENGINEERING
·
2022
·
IF 3.898
Xiaohong Zhou,Wenfeng Zhou,Wei Zhuang,Chenjie Zhu,Hanjie Ying,Hongman Zhang
Cytidine 5′-monophosphate (5′-CMP) is an essential nucleotide for additives. In this study, enhanced production of 5′-CMP was realized by the transformation of cytidine using co-immobilized di-enzymes, uridine-cytidine kinase (UCK) and acetate kinase (AcK). The immobilization yield of the enzyme had a clear correlation with the surface charges as zeta potential ( ξ ). Among them, ε -polylysine-functionalized sepharose (SA-EPL, ξ = 9.31 mV) showed high immobilization yield (78.8%), which was 4.9-fold than that of nitrilotriacetic acid functionalized sepharose (SA-NTA, ξ = −12.6 mV). The residual activity of affinity co-immobilized enzyme (EPL-Ni/ [email protected] ) was higher than 70.6% after recycled 10 times. Thus, this study provides an effective approach for the production of 5′-CMP with the advantages of low adenosine 5′-triphosphate (ATP) consumption, reduced side reactions, and improved reusability by co-immobilized UCK and AcK on the functionalized Sepharose.
研究领域:
生物技术
·
生物化学
·
酶学
✓ 已验证
产品关联
DOI
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 42
·35991-35999
·
IF 3.289
Jing Liu,Jing Liu,Dujuan Zhao,Naxin Ma,Yuxia Luan
Cytarabine (1-β-D-arabinofuranosylcytosine, Ara-C), an attractive medicinal treatment for myeloblastic leukemia, is subject to low oral bioavailability due to its weak membrane permeability and lipophilicity as well as its poor metabolic stability. Based on these considerations, we proposed a chemical linkage of cytarabine with lauric acid (LA), a long-chain fatty acid with 12 carbons, leading to a new prodrug, LA–Ara. The NH2 group of Ara-C is protected by conjugation and thus cannot not be deactivated by deamination; moreover, notably high liposolubility and penetrability were obtained. When dispersed in water, this new amphiphilic molecule can adopt a nanofiber configuration. It was found that LA–Ara molecules are stable in artificial biological media, indicating that the prodrug could be administrated orally. MTT assays on HL60 and K562 cells were performed, and the significantly higher cytotoxicity compared to the pure drug suggested that the prodrug has conspicuously superior antiproliferative activity. Following oral administration, the elimination half-life and bioavailability of the LA–Ara group dramatically increased to 6.6- and 32.8-fold of those of free Ara-C, respectively. It appears that this new prodrug could be an effective oral alternative treatment to Ara-C and supply a promising therapy index for leucocythemia.
研究领域:
药理学
·
肿瘤学
·
药物化学
✓ 已验证
产品关联
DOI
高影响因子
Pharmaceutics
·
2024
·Vol. 16
·期 9
·1220
·
IF 4.9
Chunxia Zhu,Yang Liu,Xiaojun Ji,Yaxuan Si,Xianhao Tao,Xiaohua Zhang,Lifang Yin
Background:Acute myeloid leukemia (AML) is the most common type of acute leukemia among adults with the recommend therapy of combination of cytarabine and idarubicin in the induction phase. The uncoordinated pharmacokinetics prevent adequate control of drug ratio following systemic administration. Therefore, the dual-loaded liposomes containing cytarabine and idarubicin for synergistic effects were proposed and investigated.Methods:The molar ratio of cytarabine and idarubicin for synergistic effects was investigated. The dual-loaded liposomes were prepared and characterized by particle size, zeta potential, encapsulation efficiency, cryo-Transmission electron microscopy (cryo-TEM), and in vitro stability. The in vitro cytotoxicity and cell uptake of liposomes were determined within CCRF-CEM cells. The PK experiments was carried out in male SD rats. The in vivo antitumor effect was carried out within CD-1 nude female mice. The antitumor mechanism of liposomes was investigated.Results:The synergistic molar ratios were found to be in the range of 20:1~40:1. The size distribution of the dual-loaded liposomes was approximately 100 nm with PDI ≤ 0.1, a zeta potential of approximately −30 mV, an entrapment efficiency of cytarabine and idarubicin of >95% with spherical structure and uniform distribution, and in vitro stability for 21 d. The drugs in the liposomes can be quickly uptaken by the leukemia cells. The PK experiments showed that the molar ratio of cytarabine to idarubicin in plasma was maintained at 30:1 within 4 h. The efficacy of liposomes was significantly enhanced. Conclusions: The dual-loaded liposomes containing cytarabine and idarubicin showed enhanced antitumor efficacy.
研究领域:
药理学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）