Frontiers in Pharmacology
·
2022
·
IF 5.988
Chen Bing,Xu Dafen,Li Zhijun,Jing Yafei,Lin Luping,Li Shaoguang,Huang Liying,Huang Xiuwang,Liu Ailin,Lin Xinhua,Yao Hong
Selaginella doederleinii Hieron is a traditional Chinese medicinal herb widely used to treat different cancers. Previously, we showed that the total bioflavonoid extract of S. doederleinii (TBESD) exhibits anti-carcinogenic activities both in vitro and in vivo. However, the plasma protein binding and pharmacokinetics parameters of TBESD remain unclear. To investigate plasma protein binding, tissue distribution, and excretion of TBESD, rats were administered a single dose of TBESD (600 mg/kg) intragastrically and tissue distribution and excretion of TBESD components were determined by rapid high-performance liquid chromatography and tandem mass spectrometry. TBESD binding to human serum albumin (HSA) was assessed by fluorescence spectroscopy. TBESD components amentoflavone, delicaflavone, robustaflavone, 2″,3″-dihydro-3′,3‴-biapigenin, and 3′,3‴-binaringenin were rapidly absorbed and distributed in various tissues, mostly in the lungs, kidneys, and ovaries, without long-term accumulation. The excretion of bioflavonoids occurred mostly via the intestinal tract and constituted 30% of the administered dose up to 48 h. Spectral analysis indicated that TBESD had a dynamic quenching effect on HSA by binding to one HSA site through hydrophobic interactions and hydrogen bond formation. This is the first comprehensive report on the tissue distribution, excretion, and plasma protein binding of TBESD. This study provides important information on TBESD pharmacokinetics necessary for its further development into a therapeutic form for clinical applications.
研究领域:
药理学
·
中药学
✓ 已验证
DOI
高影响因子
Frontiers in Pharmacology
·
2021
·
IF 5.811
Chen Bing,Luo Hongbin,Chen Weiying,Huang Qishu,Zheng Kaifan,Xu Dafen,Li Shaoguang,Liu Ailin,Huang Liying,Zheng Yanjie,Lin Xinhua,Yao Hong
Delicaflavone (DF), a natural active ingredient from Selaginella doederleinii Hieron, has been reported to have favorable anticancer effects and is thus considered a potential anticancer agent. However, its pharmacokinetics and plasma protein binding properties remain unknown. Here, we investigated the pharmacokinetic profile of DF in rats using a validated HPLC-MS/MS methods, as well as its human serum albumin (HSA) binding properties through multi-spectroscopic and in silico methods. The results showed that DF was rapidly eliminated and had a widespread tissue distribution after intravenous administration. DF showed linear dynamics in the dose range of 30–60 mg/kg and poor oral bioavailability. The major distribution tissues of DF were the liver, lungs, and kidneys. Ultraviolet and fluorescence spectroscopy and molecular docking demonstrated that DF had a static quenching effect on HSA, with one binding site, and relatively strong binding constants. Thermodynamic analysis of the binding data revealed that hydrogen bonding and van der Waals interactions played major roles in binding. The results of this study further our understanding of the pharmacokinetic and plasma protein binding properties of the potential anticancer agent DF and shed light on pharmacological strategies that may be useful for the development of novel cancer therapeutics.
研究领域:
药理学
·
肿瘤学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Yilin Wang,Xiran Zhou,Xijing Yang,Jiahao Liang,Shifan Chen,Ziyue Ling,Wenjie Wang,Zijian Shao,Xin Song,Ran Wei,Weifeng Zhao,Changsheng Zhao
Separating toxins from albumin is significantly more challenging than simply adsorbing the toxin/protein complex during blood purification. Bilirubin is distinctive among protein-bound toxins because its photodecomposition products are hydrophilic and readily dissociate from albumin. Inspired by phototherapy for neonatal jaundice, an innovative multifunctional adsorbent is proposed and equipped with self-photodecomposition and visual monitoring abilities. Herein, inverse opal beads (IOBs) is developed through strategic nanoarchitectonics. The periodic ordered structure of the IOBs imparts a self-hosted blue light emission property that facilitates the bilirubin photodecomposition. Additionally, the interconnected pores of the IOBs enhance the adsorption of bilirubin photodecomposition products. Moreover, the colors of the IOBs change in response to the amount of adsorbed bilirubin photodecomposition products, allowing for real-time visual monitoring of the adsorption state during hemoperfusion. These features allow the IOBs to effectively compete with albumin for toxin binding. In hyperbilirubinemia rats, the total bilirubin (TBIL) clearance ratios achieved by the IOBs and a commercial adsorbent (BS330) are 45.1% and 29.3%, respectively. Notably, albumin (ALB) concentration decreased by 31.8% after treatment with BS330, whereas no significant change is observed in the IOB-treated group. These results suggest that IOBs hold great potential as a highly promising adsorbent for treating hyperbilirubinemia.
研究领域:
生物医学工程
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
Nano Today
·
2024
·
IF 13.2
Fapu Wu,Senyao Liu,Bingbing Zheng,Wenwen Cao,Yu Zhu,Jieyu Yang,Hu Xiong
Real-time monitoring of intestinal movement is critical for the clinical diagnosis of bowel diseases, however, the application of organic fluorophores in non-invasive imaging of the intestinal tract via systemic administration is still challenging. We herein report a series of albumin-chaperoned chloro-cyanine dyes for high spatiotemporal tracking of intestinal peristalsis and bowel disease in vivo. By adjusting the size of the central rings, Cy7–5 , with a five-membered ring and meso-chlorine, could covalently bind with circulating endogenous albumin in the blood, generating a bright and stable cyanine-albumin fluorescent complex with ∼1055 nm fluorescence in the near-infrared-II window in situ. Notably, Cy7–5 was able to clearly view intestinal peristalsis by harnessing the inherent intestine tropism of Cy7–5 -albumin complex following intravenous (i.v.) administration. Furthermore, a hydroxyl radical (·OH)-activatable fluorophore ( Hydro-Cy7–5 ) was created, allowing for the selective detection of overproduced ·OH in bowel disease as well as the successful visualization of the inflammatory intestinal tract in vivo after i.v. injection. This work provides a facile strategy for the investigation of intestinal movement and related diseases.
研究领域:
医学影像学
·
分子生物学
·
药理学
✓ 已验证
DOI
高影响因子
Journal of BUON
·
2020
·Vol. 25
·期 2
·681-687
·
IF 1.695
Han X,Wang Z
Purpose This study aimed to investigate the efficacy of albumin-bound paclitaxel (nab-paclitaxel) in the treatment of advanced refractory breast cancer (BC) and its effect on serum resistin. Methods A retrospective study was performed based on the clinical records of 95 patients with advanced refractory BC admitted to Weihai Central Hospital from March 2012 to May 2015. Thirty-four patients were treated with traditional paclitaxel and enrolled in the control group, while the other 61 patients were treated with nab-paclitaxel and enrolled in the study group. The efficacy, toxicity and side effects, quality of life, and serum resistin levels were compared between the two groups. Results The total response rate (RR) of the study group was much higher than that of the control group (p<0.05). The leukopenia level of the study group during the treatment was significantly lower than that of the control group (p<0.05). The level of serum resistin in the study group after treatment was significantly lower than in the control group (p<0.05). The improvement rate of quality of life in the study group was significantly higher than in the control group (p<0.05). Conclusion The results indicated that nab-paclitaxel is very effective in treating advanced refractory BC and reduces the level of serum resistin. It can improve the quality of life of patients and is worthy of clinical promotion.
研究领域:
肿瘤学
·
药理学
·
癌症研究
✓ 已验证
DOI
PubMed
高影响因子
Drug Delivery and Translational Research
·
2018
·Vol. 8
·期 5
·1162-1170
·
IF 3.395
Wei Wei,He Zhonggui,Yang Jincheng,Sun Mengchi,Sun Jin
Rational design of anticancer prodrugs for efficient albumin binding can show distinct advantages in drug delivery in terms of high drug availability, long systemic circulation, potential targeting effect, and enhanced chemotherapy effect. In the present study, we reported a cytosine arabinoside (Ara-C) prodrug which could well formulate in solution and instantly transform into long-circulating nanocomplexes by hitchhiking blood-circulating albumin after i.v. administration. Specifically, Ara-C was conjugated with an albumin-binding maleimide derivative, the resulting Ara-C maleimide caproic acid conjugate (AM) was well formulated in aqueous solution, conferring high albumin-binding ability in vitro albumin-binding studies. Moreover, in vivo fluorescence images of sulfo-cyanine5 maleimide indirectly demonstrated that AM showed better accumulation in tumors, exhibiting superior tumor targeting ability and antitumor activity compared to Ara-C. Such a uniquely developed strategy, integrating high albumin-binding capability, has great potential to be applied in clinical cancer therapy.
研究领域:
药理学
·
肿瘤学
·
药物化学
✓ 已验证
DOI
高影响因子
JOURNAL OF COORDINATION CHEMISTRY
·
2021
·
IF 1.751
Yu Zhang,Yong-Hang Li,Shi-Bin Jiang,Shi-Ling Wang,Shao-Song Qian,Jie Qin,Jian-Ping Ma,Juan Li
Reactions of 2-{[5-(Pyridin-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}acetic acid (H2L) with manganese(II), zinc(II) and cadmium(II) acetate in CH3OH/H2O mixture result in the corresponding metal complexes. All the obtained complexes were characterized by IR spectroscopy, elemental analyses, ESI-MS, and single-crystal X-ray diffraction. Structural analyses reveal the dinuclear complexes with the compositions [Mn2L2(CH3OH)2(H2O)2]·2CH3OH (1), [Zn2L2(CH3OH)2(H2O)2]·2CH3OH (2), and 1D chain structure [CdL(H2O)]n (3) in all complexes, H2L is doubly deprotonated (L2-) and serves as equilibrium anion. The carboxylate acts as monodentate ligand in 1 and 2, While μ1,1-bridging ligand in 3. The measurement of Jack Bean urease inhibitory activity showed that 1 and 3 exhibited considerable inhibitory effects for Jack Bean urease with IC50 Values of 12.4 and 2.7 μM, respectively. In addition, bioactive complexes 1 and 3 can effectively bind to bovine serum albumin (BSA), which was assessed by tryptophan emission quenching measurement
研究领域:
配位化学
·
生物无机化学
·
药物化学
✓ 已验证
DOI
高影响因子
BIOMATERIALS
·
2019
·
IF 10.273
Wenjuan Zhang,Sichen Song,Hanxun Wang,Qiu Wang,Dan Li,Shunzhe Zheng,Zhuangyan Xu,Haotian Zhang,Jian Wang,Jin Sun
Tumor metastases account for about 90% of cancer-related death, among which lymphatic metastases play a pivotal role . Therefore, high-efficiency sentinel lymph node (SLN) identification is significant for lymph node (LN) metastasis diagnosis in clinic. Herein, a novel in vivo covalent albumin-binding near-infrared (NIR) fluorescent IR820-maleimide conjugate (IR-Mal) is firstly designed as a SLN dual-mode imaging agent. The IR-Mal conjugate exhibits bright blue appearance and its large Stokes shift (over 100 nm) increases the fluorescent imaging resolution effectively. The fluorescence intensity of covalent albumin-binding IR-Mal (BSA-IR-Mal) complex is considerably stronger than that of IR-Mal. In vivo , IR-Mal could rapidly covalently bind the tissue interstitial albumin following subcutaneous administration and BSA-IR-Mal complexes could specifically accumulate on LN, and detect both normal and metastatic SLN through naked-eye and fluorescence imaging with high resolution. Moreover, the light stability and enhanced fluorescence intensity of BSA-IR-Mal complex facilitates its diagnosis accuracy. These findings suggest that such in vivo irreversible albumin-binding fluorescence conjugates could serve as a new agent for dual-mode imaging and have a great potential to be applied in the SLNs imaging and diagnosis.
研究领域:
医学成像
·
肿瘤学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-18
·
IF 12.6
Huang Haoyang,Liu Shaowei,Xu Ligeng,Liang Hengrui,Wu Zihao,Chen Tianfeng,Wang Jinlin,Liu Jun
Though prescribed as first-line drugs for esophageal squamous cell cancer (ESCC) therapy, the antitumor efficacy of Nab-Paclitaxel (Nab-PTX) is still unsatisfactory owing to the limitation on the dosage and therapy duration of Nab-PTX caused by adverse effects. Inspired by the very essential role of Selenoprotein N (SelN) in mediating the calcium homeostasis and the associated redox homeostasis in cells, herein, in this essay, we screened the inhibition effect of selenium-containing drugs in different forms on ESCC cell line. Investigation on KYSE-150 cells demonstrated that Nab-PTX in combination with low dosage of LNT-SeNPs may synergistically improve its antitumor efficacy on ESCC cells through promoting the cellular apoptosis. Proteomics analysis uncovered the core synergistic mechanism of LNT-SeNPs on Nab-PTX was significantly dependent on the endoplasmic reticulum (ER) stress induced by SelN-mediated Ca 2+ -IRE1α, IRE1α(S724)-CHOP-BCL2 axis. SelN knockdown KYSE-150 cell model further confirmed the very indispensable role of SelN in mediating the synergistic effect on Nab-PTX. Moreover, in vivo evaluation on KYSE-150 tumor-bearing mice models also demonstrated the supplementation of LNT-SeNPs with low dosage during the Nab-PTX treatment may synergize the antitumor efficacy and significantly mitigate the adverse reactions or toxicity resulting from a substantial dose of Nab-PTX. Overall, along with the facile accessibility of raw materials, this study reports LNT-SeNPs as a synergistic agent to promote the antitumor efficacy of Nab-PTX, which may be translated as a wide-applicable, efficient and highly safe strategy for clinical treatment of ESCC. Graphical abstract
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 2
·880
·
IF 4.6
Huanhuan Guo,Zongguang Tai,Fang Liu,Jing Tian,Nan Ding,Zhongjian Chen,Shen Gao
Over the past decade, the dose of nanoparticles given to solid tumors has remained at a median of 0.7% of the injected dose. Most nanoparticles are trapped in a mononuclear phagocyte system (MPS), of which 85% are Kupffer cells. In our study, threshold doses of bovine serum albumin (BSA) nanoparticles were investigated for the uptake of Kupffer cells in vitro and in vivo. The antitumor effect and safety of albumin-bound paclitaxel (ABP) were improved by using threshold doses of BSA nanoparticles. We found a threshold dose of 20,000 nanoparticles per macrophage uptake in vitro and a saturation dose of 0.3 trillion nanoparticles in tumor-bearing mice. In vivo efficacy and safety evaluations demonstrated that the threshold doses of blank BSA nanoparticles could significantly improve the efficacy and safety of ABP against tumors compared with ABP alone. In this study, the delivery efficiency of ABP was improved by using blank nanoparticles to saturate Kupffer cells, which provided a new approach to studying the Kupffer cell saturation threshold and thus a new scheme for improving the curative effect of ABP.Keywords:nanoparticles;drug delivery;breast cancer;Kupffer cell;albumin-bound paclitaxel (ABP);bovine serum albumin (BSA)
研究领域:
药理学
·
肿瘤学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYST
·
2020
·Vol. 145
·期 9
·3257-3265
·
IF 3.978
Yue Li,Xinxin Xu,Liqiang Liu,Hua Kuang,Liguang Xu,Chuanlai Xu
In this study, a gold immunochromatographic assay (GICA) based on a penicillin receptor protein (PBP) is proposed to simultaneously detect penicillin, cephalosporin, and carbapenem antibiotics in milk and chicken. A mutant PBP, carboxy-terminal of the β-lactam sensor-transducer protein (BlaR-CTD, I188KS19CG24C) from Bacillus licheniformis ATCC14580 was expressed in E. coli as a soluble His-tag fusion protein. The purified BlaR-CTD mutant was labeled with colloidal gold (CG-BlaR-CTD-M) and applied to develop GICA. The GICA method was performed based on a competitive form, where the binding of the ampicillin-bovine serum albumin conjugate (Amp-BSA) to CG-BlaR-CTD-M was inhibited by free β-lactams in samples. The performance of the assay was confirmed by analysis of milk and chicken samples. The limits of detection of 21 β-lactam antibiotics met the maximum residue limits set by the European Union and China. The GICA gave results within 10 min, thus providing a rapid and reliable method for the on-site detection of multiple β-lactams in milk and chicken samples.
研究领域:
分析化学
·
食品安全
·
微生物学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2024
·
IF 14.7
Zaigang Zhou,Wenjuan Luo,Chunjuan Zheng,Haoxiang Wang,Rui Hu,Hui Deng,Jianliang Shen
Currently, the efficacy of albumin-bound paclitaxel (PTX@Alb) is still limited due to the impaired PTX@Alb accumulation in tumors partly mediated by the dense collagen distribution. Meanwhile, acquired immune resistance always occurs due to the enhanced programmed cell death-ligand 1 (PD-L1) expression after PTX@Alb treatment, which then leads to immune tolerance. To fill these gaps, we newly revealed that tamoxifen (TAM), a clinically widely used adjuvant therapy for breast cancer with mitochondrial metabolism blockade capacity, could also be used as a novel effective PD-L1 and TGF- β dual-inhibitor via inducing the phosphorylation of adenosine 5ʹ-monophosphate-activated protein kinase (AMPK) protein. Following this, to obtain a more significant effect, TPP-TAM was prepared by conjugating mitochondria-targeted triphenylphosphine (TPP) with TAM, which then further self-assembled with albumin (Alb) to form TPP-TAM@Alb nanoparticles. By doing this, TPP-TAM@Alb nanoparticles effectively decreased the expression of collagen in vitro , which then led to the enhanced accumulation of PTX@Alb in 4T1 tumors. Besides, TPP-TAM@Alb also effectively decreased the expression of PD-L1 and TGF- β in tumors to better sensitize PTX@Alb-mediated chemo-immunotherapy by enhancing T cell infiltration. All in all, we newly put forward a novel mitochondrial metabolism blockade strategy to inhibit PTX@Alb-resistant tumors, further supporting its better clinical application.
研究领域:
肿瘤学
·
药理学
·
免疫学
·
纳米技术
✓ 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）