JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2022
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IF 5.062
Fei Wang,Xuyang Li,Xialin Hu,Wenya Zhuang,Jiewei Lai,Wenchao Wang,Xuanrong Sun,Hong Wang,Qingyong Li
FLQY2 is a camptothecin derivative modified by FL118 and proved to be good antitumor activity in vitro . However, its poor solubility leads to the low therapeutic efficacy in vivo . Here, the injectable FLQY2 lyophilized powder was prepared with Kolliphor® HS 15 (HS 15), which was called HS 15-FLQY2. The preparation process of HS 15-FLQY2 was optimized by orthogonal design and the lyophilization process was investigated by single factor experiment. Moreover, the formulation was characterized, the pharmacokinetics study and the antitumor activity were carried out in vivo . As the results, HS 15-FLQY2 (1:1500, w/w) containing 5% mannitol as cryoprotectant showed good appearance and 70% entrapment efficiency. HS 15-FLQY2 revealed low particle size (<16 nm), better homogeneity (PDI <0.2) and remained stable for 24 h in water. In addition, the data of the DSC , XRD and FTIR demonstrated that FLQY2 was distributed within micelles . In vivo , the bioavailability of HS 15-FLQY2 (i.p.) was improved significantly compared with oral CD-FLQY2 (a cyclodextrin inclusion complex of FLQY2). In addition, HS 15-FLQY2 demonstrated higher tumor inhibition effect than capecitabine , confirming the possibility of treatment cancer by the delivery of FLQY2.
研究领域:
药剂学
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肿瘤学
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生物化学
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产品关联
DOI
高影响因子
Chinese Journal of Natural Medicines
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2026
·Vol. 24
·期 8
·972-986
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IF 7.5
Chao Chen,Mengqi Wan,Zhixu Zhu,Zhaoyu Xie,Yu Zhang,Tao Xu,Han Meng,Miaomiao Wu,Liangfeng Gui,Hongbo Lv,Guodong Wang,Jun Han,Hui Che
Cisplatin (DDP) remains a standard therapy for triple-negative breast cancer (TNBC), yet intrinsic or acquired resistance often limits its efficacy; here, we report that Ramulus Mori alkaloids (SZ-A), an approved botanical α -glucosidase inhibitors, synergize with DDP to suppress TNBC progression in vitro and in vivo by driving PLA2G2A-dependent ceramide accumulation. Combining SZ-A with DDP synergistically inhibits viability, clonogenicity, migration, and invasion, induces S-phase arrest and apoptosis, and attenuates tumor growth in xenograft models. Mechanistically, SZ-A directly binds to and stabilizes PLA2G2A, blocking its autophagic-lysosomal degradation, leading to accumulated PLA2G2A that suppresses fatty acid oxidation and triggers ceramide accrual via ADIPOR2 inhibition. Genetic ablation of PLA2G2A abrogates these effects. DDP further enhances SZ-A-induced PLA2G2A upregulation and ceramide accumulation, resulting amplified cytotoxicity. Our findings reveal SZ-A as a chemosensitizing agent that enhances the efficacy of DDP in TNBC.
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产品关联
DOI
高影响因子
TALANTA
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2022
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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.
研究领域:
药理学
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分析化学
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免疫学
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临床化学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
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2022
·Vol. 27
·期 13
·4019
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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
研究领域:
分析化学
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医学诊断
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药学
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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）