JOURNAL OF ETHNOPHARMACOLOGY
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2019
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IF 3.414
Bin Xie,Yuan-Yuan Lu,Zhuo-Hui Luo,Zhao Qu,Chun-Ge Zheng,Xin-An Huang,Hong-Yan Zhou,Ying-Jie Hu,Xiao-Ling Shen
Ethnopharmacological relevance Marsdenia tenacissima (Roxb.) Wight et Arn is a vine distributed in southwest area of China and used in folk medicine for treatment of tumors. Recent decades of studies on this plant reveal its synergistic effects with certain anticancer drugs in cancer therapy. In our previous study, an extract ETA which contains total aglycones made from M. tenacissima significantly enhanced antitumor activity of paclitaxel in tumor-bearing mice. However, the effective constituents in ETA and the underlying mechanisms remain unclear. Aim of the study Reveal the active components in ETA as well as the molecular mechanism in enhancing antitumor efficacy of paclitaxel. Material and methods Main constituents in ETA were purified by chemical methods. Effects of the purified constituents on metabolic activity of CYP450 enzymes were evaluated in human liver microsomes. Ability of the constituents to enhance antitumor activity of paclitaxel were investigated in nude mice bearing HeLa tumors. Pharmacokinetic study was performed in SD rats . Molecular docking was carried out for investigation of drug-protein interactions. Results Three main C 21 steroidal aglycones, 11α- O -tigloyl-12β- O -acetyl-tenacigenin B ( MT1 ), 11α- O -2-methylbutanoyl-12β- O -tigloyl-tenacigenin B ( MT2 ) and 11α- O -2-methylbutanoyl-12β- O -acetyl-tenacigenin B ( MT3 ), together with tenacigenin B ( MT4 ) was prepared from ETA. Among them, MT1 , MT2 and MT3 strongly inhibit the metabolic activity of CYP3A4 . MT2 also showed inhibitory effects on CYP2C8 , CYP2B6 and CYP2C19 . In HeLa tumor xenografts, MT1 , MT2 and MT3 (30 mg/kg) did not affect tumor growth themselves, but significantly enhanced paclitaxel-induced growth inhibition. In addition, coadministration of MT2 with paclitaxel resulted in significant reduction of liver CYP2C8. In pharmacokinetic study, MT2 significantly increased the blood concentration of paclitaxel with increased AUC value by 2.2–5.3 folds. Molecular docking analysis suggested hydrophobic interaction modes of tenacigenin B derivatives with CYP3A4, and also the essential roles of the C-11 and C-12 ester groups for effective interaction with CYP3A4. Conclusion Our study proves that, 11α- O -tigloyl-12β- O -acetyl-tenacigenin B, 11α- O -2-methylbutanoyl-12β- O -tigloyl-tenacigenin B and 11α- O -2-methylbutanoyl-12β- O -acetyl-tenacigenin B, which are the main constituents of ETA, are active inhibitors of CYP3A4 with potential to increase therapeutic efficacy of anticancer drugs that are substrates of CYP3A4. Tenacigenin B derivatives with C-11 and C-12 ester group substitutions, or at least a large part of them, are active components in ETA and M. tenacissima to enhance in vivo antitumor efficacies of paclitaxel.
研究领域:
药理学
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肿瘤学
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民族药理学
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生物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
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2024
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IF 6.8
Xin Xiang,Chuning Dong,Lianbo Zhou,Jun Liu,Zachary M. Rabinowitz,Yuzhao Zhang,Honghui Guo,Feng He,Xingdou Chen,Yunhua Wang,Lina Cui,Xiaowei Ma
Real-time detection of cellular senescence remains a clinical challenge. Here, we aimed to develop a positron emission tomography (PET) imaging probe targeting senescence-associated β-galactosidase (SA-β-Gal), the most widely used biomarker of cellular senescence, and investigate its performance for real-time in vivo quantitative detection of cellular senescence. A stable PET imaging agent [68Ga]Ga-BGal was obtained with a high labeling yield (90.0 ± 4.3%) and a radiochemical purity (>95%). [68Ga]Ga-BGal displayed high sensitivity and specificity for β-Gal both in vitro and in vivo. The reaction and uptake of the probe correlated with the β-Gal concentration and reaction time. In PET imaging, high β-Gal-expressing CT26.CL25 tumors and doxorubicin-treated HeLa tumors showed high signals from [68Ga]Ga-BGal, while a low signal was observed in CT26.WT and untreated HeLa tumors. In summary, we showcased successful PET imaging of senescence in preclinical models using probe [68Ga]Ga-BGal. This finding holds the potential for translating senescence imaging into clinical applications.
研究领域:
医学影像学
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分子生物学
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肿瘤学
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放射学
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药学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
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2022
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IF 0
Mengsi Zhang,Lu Wang,Heng Liu,Ze Wang,Wenjie Feng,Hao Jin,Shuwei Liu,Shijie Lan,Yi Liu,Hao Zhang
Phototherapy, such as photodynamic therapy (PDT) and photothermal therapy (PTT), refers to the therapeutic strategy using a visible or near-infrared (NIR) laser to generate free radicals or heat for noninvasive and localized tumor treatment. However, limited by the low photoconversion efficiency of therapeutic agents, a single treatment method can hardly lead to complete tumor ablation, even when enhancing the power density of the laser and/or prolonging the irradiation duration. In this work, copper ion and ruthenium complex codoped polydopamine nanoparticles (Cu(II)/LRu/PDA NPs) are designed for PDT/PTT dual-mode therapy. The doped LRu in the NPs can generate reactive oxygen species under visible laser irradiation and enable PDT. Because of the strong absorption in the NIR region, PDA can not only generate heat for PTT under irradiation but also be used for photoacoustic tomography (PAT) imaging. Meanwhile, the doping of Cu(II) in the NPs through the coordination with PDA facilitates T1-weighted magnetic resonance imaging (MRI). Thus, MR/PAT imaging-guided PDT/PTT dual-mode therapy is achieved. The in vivo experiments indicate that the Cu(II)/LRu/PDA NPs can accumulate in HeLa tumors with a retention rate up to 8.34%ID/g. MR/PAT imaging can clearly identify the location and boundary of the tumors, permitting precise guidance for phototherapy. Under the combined effect of PDT and PTT, a complete ablation of HeLa tumors is achieved. The current work provides an alternative nanoplatform for performing PDT/PTT dual-mode therapy, which can be further guided by MR/PAT imaging.
研究领域:
纳米技术
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生物医学工程
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癌症治疗
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医学成像
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产品关联
DOI
PubMed
ACS Applied Materials & Interfaces
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2019
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IF 8.456
Xiaoli Hu,Chetry Mandika,Lizhen He,Yuanyuan You,Yanzhou Chang,Jing Wang,Tianfeng Chen,Xueqiong Zhu
Rational design and construction of theranostic nanomedicines based on clinical characteristics of cervical cancer is an important strategy to achieve precise cancer therapy. Herein, we fabricate a cervical cancer-targeting gold nanorod-mesoporous silica heterostructure for codelivery of synergistic cisplatin and antiangiogenic drug Avastin (cisplatin–AuNRs@SiO2–Avastin@PEI/AE105) to achieve synergistic chemophotothermal therapy. Based on database analysis and clinical sample staining, conjugation of the AE105-targeting peptide obviously improves the intracellular uptake of the nanosystem and enhances the cancer-killing ability and selectivity between cervical cancer and normal cells. It could also be used to specifically monitor the urokinase-type plasminogen activator receptor (uPAR) expression level in clinical cervical specimens, which would be an early indicator of prognosis in cancer treatment. Under 808 nm laser irradiation, the nanosystem demonstrates smart NIR-light-triggered drug release and prominent photodynamic activity via induction of reactive oxygen species overproduction-mediated cell apoptosis. The nanosystem also simultaneously suppresses HeLa tumor growth and angiogenesis in vivo, with no evident histological damage observed in the major organs. In short, this study not only provides a clinical data-based rational design strategy of smart nanomedicine for precise treatment and rapid clinical diagnosis of cervical cancer but also contributes to the development of the clinical translation of nanomedicines.
研究领域:
纳米技术
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癌症治疗
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药学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
ACS Nano
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2024
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IF 15.8
Jianshuai Bao,Jiefei Wang,Sudi Chen,Shiqi Liu,Zhen Wang,Weiwei Zhang,Chenhui Zhao,Yuling Sha,Xiaoyan Yang,Yusen Li,Yong Zhong,Feng Bai
Reactive oxygen species (ROS) mediated tumor cell death is a powerful anticancer strategy. Cuproptosis is a copper-dependent and ROS-mediated prospective tumor therapy strategy. However, the complex tumor microenvironment (TME), low tumor specificity, poor therapy efficiency, and lack of imaging capability impair the therapy output of current cuproptosis drugs. Herein, we designed a dual-responsive two-dimensional metal–organic framework (2D MOF) nanotheranostic via a coordination self-assembly strategy using Au(III) tetra-(4-pyridyl) porphine (AuTPyP) as the ligand and copper ions (Cu2+) as nodes. The dual-stimulus combined with the protonation of the pyridyl group in AuTPyP and deep-penetration ultrasound (US) together triggered the controlled release in an acidic TME. The ultrathin structure (3.0 nm) of nanotheranostics promoted the release process. The released Cu2+ was reduced to Cu+ by depleting the overexpressed glutathione (GSH) in the tumor, which not only activated the Ferredoxin 1 (FDX1)-mediated cuproptosis but also catalyzed the overexpressed hydrogen peroxide (H2O2) in the tumor into reactive oxygen species via Fenton-like reaction. Simultaneously, the released AuTPyP could specifically bind with thioredoxin reductase and activate the redox imbalance of tumor cells. These together selectively induced significant mitochondrial vacuoles and prominent tumor cell death but did not damage the normal cells. The fluorescence and magnetic resonance imaging (MRI) results verified this nanotheranostic could target the HeLa tumor to greatly promote the self-enhanced effect of chemotherapy/cuproptosis and tumor inhibition efficiency. The work helped to elucidate the controlled assembly of multiresponsive nanotheranostics and the high-specificity ROS regulation for application in anticancer therapy.
研究领域:
纳米技术
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癌症治疗
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材料科学
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生物医学工程
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化学
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药学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2019
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IF 8.456
Yeneng Dai,Jinzhong Su,Kun Wu,Wenkang Ma,Bing Wang,Meixing Li,Pengfei Sun,Qingming Shen,Qi Wang,Quli Fan
Multifunctional theranostic nanoplatforms (NPs) in response to environment stimulations for on-demand drug release are highly desirable. Herein, the near-infrared (NIR)-absorbing dye, indocyanine green (ICG), and the antitumor drug, doxorubicin (DOX), were efficiently coencapsulated into the thermosensitive liposomes based on natural phase-change material. Folate and conjugated gadolinium (Gd) chelate-modified liposome shells enhance active targeting and magnetic resonance performance of the NPs while maintaining the size of the NPs. The ICG/DOX-loaded and gadolinium chelate conjugated temperature-sensitive liposome nanoplatforms (ID@TSL-Gd NPs) exhibited NIR-triggered drug release and prominent chemo-, photothermal, and photodynamic therapy properties. With the coencapsulated ICG, DOX, and the conjugated gadolinium chelates, the ID@TSL-Gd NPs can be used for triple-modal imaging (fluorescence/photoacoustic/magnetic resonance imaging)-guided combination tumor therapy (chemotherapy, photothermotherapy, and photodynamic therapy). After tail vein injection, the ID@TSL-Gd NPs accumulated effectively in subcutaneous HeLa tumor of mice. The tumor was effectively suppressed by accurate imaging-guided NIR-triggered phototherapy and chemotherapy, and no tumor regression and side effects were observed. In summary, the prepared ID@TSL-Gd NPs achieved multimodal imaging-guided cancer combination therapy, providing a promising platform for improving diagnosis and treatment of cancer.
研究领域:
癌症治疗
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纳米技术
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生物医学工程
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药学
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医学成像
✓ 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）