PHYTOMEDICINE
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2025
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IF 8.3
Yao-lei Ma,Xiao-wei Huo,Colin Wong,Feng-jie Zhou,Shan-ze Li,Han Zhang,Wei Lei
Background Although doxorubicin (DOX) is a highly efficient antineoplastic chemotherapeutic drug, it greatly increases the risk of heart damage. Salvianolic acid A (SAA), a water-soluble active component from traditional Chinese medicine Salvia miltiorrhiza Bunge, is shown to exert various cardioprotective effects. However, the potential of SAA in protecting DOX-induced cardiotoxicity (DIC) and its underlying mechanisms have yet to be elucidated. Purpose In the current study, we aimed to identify the targets and investigate the cardioprotective mechanism of SAA improving DIC. Methods we established DIC mice to evaluate the cardioprotective effects of SAA by pharmacodynamics, myocardial metabolomic and protomics analysis. Multipe protein-small molecule interaction strategies including surface plasmon resonance, microscale thermophoresis and cellular thermal shift assay, combined with target-depleted cell and animal models were applied for identifying potential targets of SAA. For clinical translation, we also investigated cardioprotective activities of SAA in DOX-treated lewis lung carcinoma-bearing mice. Results SAA significantly alleviated cardiomyocyte apoptosis and oxidative damage, and improved echocardiographic parameters in DIC mice. In addition, myocardium metabolomic and proteomics analysis revealed that SAA preserved hearts by modulating L-Glutamic acid, L-Aspartic acid, citrate and isocitrate and restoring glutamic-oxaloacetic transaminase 2 (GOT2) expression. With the help of multipe protein-small molecule interaction strategies, GOT2 was identified as one of the targets of SAA, and a strong affinity was characterized with a dissociation constant of 1.712 μM. SAA ameliorated DOX-induced oxidative damage, mitochondrial respiration suppression, mitochondrial membrane potential loss and NADH levels, which were validated in GOT2 knockdown H9C2 cells. In GOT2 depleted zebrafish, SAA did not display a protective effect against DIC, while in lewis lung carcinoma-bearing mice, SAA not only improved DIC, but also exerted combined anti-tumor effects with DOX. Conclusion SAA targets GOT2 to alleviate myocardial oxidative stress by regulating malate-aspartate NADH shuttle, thereby protecting against DIC. Our findings highlighted the therapeutic potential of activating GOT2 in mitigating DIC and the possibility of SAA and DOX-based combination therapy.
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高影响因子
RSC Advances
·
2013
·Vol. 3
·期 45
·23133-23138
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IF 2.562
Yang Wang,Yun Xiao,Hangyu Zhou,Wei Chen,Ruikang Tang
A novel versatile system combining chemotherapy and photothermal therapy for cancer cells using CuS NCs is reported. CuS NCs were synthesized by a solid–liquid reaction between Cu2O nanocubes and thiourea. While the hollow nanocage can be used to load anticancer drugs for chemotherapy, the CuS can convert NIR light into heat for photothermal therapy. More importantly, CuS NCs display exceptionally high drug loading capacity of DOX with 500 wt% and release of DOX is pH-controllable, which is a spontaneous process under intracellular conditions. Compared with chemotherapy or photothermal therapy alone, the combination of chemotherapy and phototherapy can significantly improve the therapeutic efficacy. This improvement strategy using multifunctional nanomaterials may be particularly useful in biomedical applications.
研究领域:
肿瘤学
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纳米医学
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药物递送
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转化医学
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生物材料
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BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
·
2026
·Vol. 1870
·期 11
·130988
·
IF 2.9
Jingxian Han,Lei Hua,Siqi Zhang,Bin Yang,Zhiying Li,Xiangguang Meng
Background Heart failure (HF) remains a leading cause of death worldwide. Stem cells represent a promising strategy for myocardial regeneration due to their differentiation potential and paracrine effects. This study investigated the effect of human pericardial fluid Sca-1 + /Nanog + cells Conditioned Medium (hPFCs-CM) on doxorubicin (DOX)-induced damage to AC16 cardiomyocytes using transcriptomic analysis. Methods Human AC16 cardiomyocytes were divided into Control (CON), DOX, DOXh, and hPFCs groups. Cell viability, cytotoxicity (LDH release), reactive oxygen species (ROS) levels, and apoptosis were assessed. Transcriptomic sequencing was performed on CON, DOX, and DOXh groups. MYH3 and IFI16 genes were knocked down using siRNA, followed by Western blot analysis of apoptosis. Results DOX significantly increased ROS and apoptosis compared with CON group ( P < 0.05), while hPFCs-CM attenuated these effects ( P < 0.05). RNA-seq identified 52 differentially expressed genes between DOX and DOXh groups (adj P < 0.05). Three target genes ( MYH3 , IFI16 , and KCTD14 ) were selected for RT-qPCR validation. Further functional assays revealed that MYH3 knockdown significantly potentiated the anti-apoptotic activity of hPFCs-CM ( P < 0.05), whereas IFI16 knockdown showed no significant effect. Conclusion hPFCs-CM effectively attenuated DOX-induced AC16 cardiomyocyte damage through MYH3, providing potential molecular targets for future mechanistic studies in myocardial injury treatment.
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Cardiovascular Toxicology
·
2026
·Vol. 26
·期 9
·98
·
IF 3.3
Hou Qian,Yu Xinyue,Wu Ke,Chen Siling,Mao Xin,Qian Xinying,Li Changjin,Sheng Lidan,Wang Ruiping,Huang Yin
The clinical utility of doxorubicin (DOX) is severely limited by dose-dependent cardiotoxicity, for which effective interventions remain scarce. Huangqi Guizhi Wuwu Decoction (HGWD) shows promising cardioprotective potential, but its mechanisms against DOX-induced cardiotoxicity (DIC) remain unexplored. This study explored the molecular mechanisms using an integrated metabolomics and transcriptomics approach. We identified 57 compounds in HGWD by liquid chromatography ion trap time-of-flight mass spectrometry (LC-IT-TOF/MS), and quantified five representative compounds for standardization. Mice were randomized into six groups: control, DOX (10 mg/kg × 2), DOX + low-dose HGWD (7 g/kg/d), DOX + high-dose HGWD (14 g/kg/d), DOX + dexrazoxane (100 mg/kg × 2), and HGWD (14 g/kg/d) alone. HGWD effectively alleviated cardiac dysfunction and reduced serum injury markers, with the high-dose group demonstrating efficacy comparable to the positive control drug, dexrazoxane. Subsequently, multi-omics profiling was performed on heart tissues from the control, DOX, and DOX + high-dose HGWD groups. Metabolomics identified 31 differential metabolites, highlighting energy metabolism restoration (e.g., acylcarnitines, citric acid) and inflammatory mediator modulation (e.g., arachidonic acid). Transcriptomics uncovered 37 genes enriched in innate immunity (e.g., Irf7 , Isg15 ) and apoptosis (e.g., Bax , Cdkn1a ). Network analysis constructed a core regulatory module, pinpointing CDKN1A as a potential mediator. Validation experiments confirmed that HGWD suppressed DOX-induced CDKN1A upregulation in mouse hearts. Furthermore, in H9c2 cells, HGWD mitigated DOX-induced apoptosis and inflammation, exhibiting cytoprotection comparable to pifithrin-α, a specific p53 inhibitor. In summary, HGWD protects against DIC by modulating a multi-target network and the suppression of CDKN1A represents a key underlying mechanism. Graphical
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International Journal of Polymeric Materials and Polymeric Biomaterials
·
2017
·
IF 1.515
Hu Zou,Hui Liu
Dual-responsive amphiphilic random copolymer containing tri(ethylene glycol)methyl ether methacrylate (MEO3MA) and 1′-(2-acryloxyethyl)-3′,3′-dimethyl-6-nitrospiro-(2H-1-benzopyran-2,2′-indoline) (SPMA) was successfully synthesized by atom transfer radical polymerization. The temperature and photo dual stimuli-responsive behaviors were investigated by lower critical solution temperature testing and UV–Vis absorption spectra, and their self-assembly morphology at various conditions was observed via TEM. The accumulative release of doxorubicin at all the conditions increased with the prolonging dialysis time, and it attained the highest value when the two chain segments of the copolymer underwent their hydrophobic/hydrophilic transition (50°C and UV light irradiation).
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PHYTOMEDICINE
·
2022
·
IF 6.656
Linhao Xu,Daqiang He,Yirong Wu,Lishui Shen,Yongmei Wang,Yizhou Xu
Background Heart failure (HF) is a common cardiovascular syndrome. Tanshinone IIA (Tan IIA) is a pharmacologically active monomer that exerts a significant cardioprotective effect in the clinic; however, the specific mechanisms are not fully understood. Purpose We mainly investigated the protective effects of Tan IIA on doxorubicin (DOX)-induced HF. Methods In an in vitro study, H9C2 and HL-1 cells were cultured and treated with DOX and Tan IIA for 24 h, we investigated the mechanism underlying Tan IIA-mediated protection. In an in vivo study, a model of DOX-induced HF was established in C57BL/6 mice that were divided into the six groups randomly: a control group, a DOX group, DOX groups treated with Tan IIA (DOX+Tan IIA) at dosages of 2.5, 5 and 10 mg/kg/day and DOX groups treated with N-acetylcysteine (NAC) at dosages of 200 mg/kg/day. Result The results demonstrated that Tan IIA significantly increased cell viability and protected against DOX-induced apoptosis. RNA-sequencing showed that the genes expression associated with the apoptotic signaling pathway was altered by Tan IIA. Among the differentially expressed genes, death-domain associated protein (DAXX), which plays an critical role in apoptotic signaling, exhibited increased expression under Tan IIA treatment. In addition, RNA interference was used to silence the expression of DAXX, which abolished Tan IIA-mediated protection against DOX-induced apoptosis; this effect was associated with extracellular signal-regulated protein kinase 1/2 (ERK1/2) and mitogen-activated protein kinase (MEK) expression. In the in vivo study, the echocardiography results revealed that heart function was rescued by Tan IIA, and the histomorphology results showed that Tan IIA prevented myocardial structural alteration and myofibril disruption. Furthermore, Tan IIA induced the expressions of DAXX, p-ERK1/2 and p-MEK. Tan IIA also inhibited apoptosis by suppressing the expression of cleaved caspase-8, p-P38 and cleaved caspase-3. Conclusion Our results provide novel interpretations into the important role of DAXX in DOX-induced cardiotoxicity and show that Tan IIA may be a novel agent strategy for HF treatment via activating the DAXX/MEK/ERK1/2 pathway.
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ACS Applied Bio Materials
·
2021
·
IF 0
Dandan Ren,Gareth R. Williams,Yanyan Zhang,Rong Ren,Jiadong Lou,Li-Min Zhu
Bringing together photothermal therapy and chemotherapy (photothermal-chemotherapy, PT-CT) is a highly promising clinical approach but requires the development of intelligent multifunctional delivery vectors. In this work, we prepared mesoporous polydopamine nanoparticles (MPDA NPs) loaded with the chemotherapeutic drug doxorubicin (DOX). These NPs were then coated with the platelet membrane (PLTM). The coated MPDA NPs are spherical and clearly mesoporous in structure. They have a particle size of approximately 184 nm and pore size of ca. 45 nm. The NPs are potent photothermal agents and efficient DOX carriers, with increased rates of drug release observed in vitro in conditions representative of the tumor microenvironment. The NPs are preferentially taken up by cancer cells but not by macrophage cells, and while cytocompatible with healthy cells are highly toxic to cancer cells. An in vivo murine model of human breast cancer revealed that the NPs can markedly slow the growth of a tumor (ca. 9-fold smaller after 14 days’ treatment), have extended pharmacokinetics compared to free DOX (with DOX still detectable in the bloodstream after 24 h when the NPs are applied), and are highly targeted with minimal off-site effects on the heart, liver, spleen, kidney, and lungs.
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ACS Biomaterials Science & Engineering
·
2021
·
IF 4.749
Chuhang Zhou,Xinping Hu,Qi Liu,Leqi Wang,Yuanhang Zhou,Yao Jin,Yining Ma,Yan Liu
Cancer-associated fibroblasts (CAFs) were believed to establish a tight physical barrier and a dense scaffold for tumor cells to make them maintain immunosuppression and drug resistance, strongly hindering nanoparticles to penetrate into the core of tumor tissues and limiting the performance of tumor cell-targeted nanoparticles. Here, we fabricated the substrate Z-Gly-Pro of fibroblast activation protein α (FAPα) and folic acid-codecorated pH-responsive polymeric micelles (dual ligand-modified PEOz-PLA polymeric micelles, DL-PP-PMs) that possessed nanodrill and tumor cell-targeted functions based on Z-Gly-pro-conjugated poly(2-ethyl-2-oxazoline)-poly(D,l-lactide) (ZGP-PEOz-PLA), folic acid (FA)-conjugated PEOz-PLA (FA-PEOz-PLA), and PEOz-PLA for cancer therapy. The micelles with about 40 nm particle size and a narrow distribution exhibited favorable pH-activated endo/lysosome escape induced by their pH responsibility. In addition, the enhancement of in vitro cellular uptake and cytotoxicity to folate receptors or FAPα-positive cells for doxorubicin (DOX)/DL-PP-PMs compared with DOX/PP-PMs evidenced the dual target ability of DOX/DL-PP-PMs, which was further supported by in vivo biodistribution results. As expected, in the human oral epidermal carcinoma (KB) cells xenograft nude mice model, the remarkable enhancement of antitumor efficacy for DOX/DL-PP-PMs with low toxicity was observed compared with DOX/FA-PP-PMs and DOX/ZGP-PP-PMs. The possible mechanism was elucidated to be the dismantling of the stromal barrier by nanodrill-like DOX/DL-PP-PMs via the deletion of CAFs evidenced by the downregulation of α-SMA and inhibition of their functions proved by the decrease in the microvascular density labeled with CD31 and the reduction in the extracellular matrix detected by the collagen content, thereby promoting tumor penetration and enhancing their uptake by tumor cells. The present research offered an alternative approach integrating anticancer and antifibrosis effects in one delivery system to enhance the delivery efficiency and therapeutic efficacy of anticancer drugs.
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JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2021
·Vol. 73
·期 8
·1128-1135
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IF 3.765
Li Guo,Meng Fayan,Lu Taicheng,Wei Liying,Pan Xin,Nong Zhenzhen,Wei Mei,Liao Chuanan,Li Xuehua
ObjectiveMolybdenum disulfide (MoS2) has been developed for medical uses due to its excellent medically beneficial characteristics. This research was designed to develop a multifunctional nano-drug delivery system based on the nano-structure of MoS2 for combined chemo/gene/photothermal therapy targeting multidrug-resistant cancer.MethodsMoS2 nanosheets were prepared by a hydrothermal reaction and modified. Afterward, the nanocarrier was characterised. In vitro cytotoxicity of the drug delivery systems on human breast adenocarcinoma cell lines was assessed.Key findingsThe nanocarrier was a flake-like structure with a uniform hydrodynamic diameter and possessing good colloidal stability. The nanocarrier showed the capacity to be deployed for co-delivery of Doxorubicin (DOX) and siRNA. The release of DOX could be triggered and enhanced by pH and application of near-infrared (NIR) laser. The nanocarrier had a good photothermic response and stability. The nanocarrier had little effect on the cells and exhibited good biocompatibility. Measurement of the therapeutic efficacy showed that synergistic therapy combining chemo-, gene- and photothermal therapy deploying this drug delivery system will achieve a better anticancer effect on drug-resistant cancer cells than DOX alone.ConclusionsOur results suggest that this drug delivery system has potential application in the therapeutic strategy for drug-resistant cancer.
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JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
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2021
·
IF 3.517
Hongdan Shen,Quan Liu,Deju Liu,Shasha Yu,Xiao Wang,Mingbo Yang
The purpose of this study was to develop a novel drug-polymer conjugation (mPEG-b-PCL-DOX) and study on its toxicity, bio-safety, and in vitro antitumor activity of mPEG-b-PCL-DOX. The polymer methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) (mPEG-b-PCL) was prepared by ring-opening polymerization. Then, succinic anhydride was reacted with mPEG-b-PCL via esterification reaction to produce mPEG-b-PCL-COOH. Finally, the polymer mPEG-b-PCL-DOX was obtained by conjugating DOX to mPEG-b-PCL-COOH by amidation. The Fourier transform infrared spectroscopy (FTIR) and 1H nuclear magnetic resonance (1H NMR) spectra were used to study the structures of obtained polymers. Transmission electron microscope (TEM) and Dynamic laser scattering (DLS) were employed to monitor the morphology and size distribution of mPEG-b-PCL-DOX nanoparticles (NPs). The mPEG-b-PCL-DOX NPs were administrated to KM rats by intraperitoneal injection to study the bio-safety of final NPs. The cell uptake and in vitro anti-tumor activity of final NPs were carried out with HCT116 cells as models. FTIR and 1H NMR spectra confirmed the obtaining of mPEG-b-PCL-DOX. The fabricated NPs were in round shapes with an average diameter of 300 nm. These NPs did not induce hemolysis and physiological or pathological changes in rats’s organs. Finally, cell teats showed that these NPs could be endocytosed by HCT 116 cells, and they had better anti-tumor effects than free DOX did. Therefore, the mPEG-b-PCL-DOX NPs had a potential application in anti-cancer therapy.
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MOLECULAR PHARMACEUTICS
·
2020
·
IF 4.321
Zhengzhong Wu,Bin Chen,Ziying Gan,Fan Chen,Xianglin Luo
The effective accumulation at tumor sites and endocytosis by tumor cells for anticancer agents in carriers are essential in successful cancer therapy, and both of the processes are affected by the surface charge of drug carriers. In this study, vitamin C (VC) was employed as an “exogenous switch” to trigger the surface charge conversion of DOX-loaded micelles to obtain a better antitumor effect. T micelles formed by poly(ε-caprolactone)-b-poly(N,N-diethylaminoethyl methacrylate)-ss-b-poly(2-methacryloyloxyethyl phosphorylcholine) (PCL–PDEA-ss-PMPC) turned their ζ potentials from +1 mV to +18 mV under treatment of 20 mM VC, while the ζ potentials of control R micelles formed by PCL-ss-P(DEA-r-MPC) almost remained unchanged under the same condition. DOX-loaded T@DOX and R@DOX had high DLCs of 12% and 13.8%, respectively, and both showed an accelerated drug release in a reductive environment (10 mM GSH or 20 mM VC) at pH 5.0. Notably, due to the surface charge conversion and fast drug release triggered by VC, T@DOX/VC (T@DOX was pretreated by VC) showed an enhanced cytotoxicity and cellular uptake superior to T@DOX, R@DOX, and R@DOX/VC. T@DOX/VC also displayed the in vivo antitumor effect well, which was comparable to DOX·HCl but with less toxic side effects than DOX·HCl. In summary, VC as an exogenous trigger can induce a better antitumor effect of drug-loaded micelles with a suitable polymer structure by charge conversion, and T@DOX/VC has shown to be as a promising approach to achieve potent treatment of tumors.
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FOOD CHEMISTRY
·
2023
·
IF 8.8
Abdur Raheem Aleem,Rihui Chen,Tonghua Wan,Wei Song,Chuyan Wu,Xue Qiu,Qiuqiang Zhan,Kuncheng Xu,Xin Gao,Tianci Dong,Xiang Chen,Lin Yu,Hongli Wen
Antibiotic detection is crucial and challenging because the widespread consumption of antibiotics have shown extensive harmful effects on food, environment and human health. Here, we propose highly water-soluble and biocompatible hyaluronic acid (HYA) functionalized upconversion nanoparticles (UCNPs) for ratiometric detection of multiple antibiotics possibly within 1 min. The UV upconversion luminescence (UCL) from UCNPs was significantly quenched by nitrofurazone/nitrofurantoin, and blue UCL was quenched by doxorubicin, while red UCL remained unchanged for internal reference. The UCNPs-HYA nanoprobes exhibit excellently sensitive and selective nitrofurazone (NFZ), nitrofurantoin (NFT) and doxorubicin (DOX) detection in linear range of 2.5–100 μM, 2.5–80 μM, and 2.5–200 μM with the LOD at 0.27 μM (55 μg/kg), 0.20 μM (48 μg/kg) and 0.17 μM (97 μg/kg), respectively. The nanoprobes achieved detecting real samples of NFZ in lake water, liquid milk and chicken meat with satisfactory results, and UCL bioimaging of doxorubicin sensing in HeLa cells.
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