Materials Science & Engineering C-Materials for Biological Applications
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2019
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IF 4.959
Jie Zhou,Qiaolei Wang,Shizhen Geng,Rui Lou,Qianwen Yin,Weiran Ye
To tackle the barrier of the insufficient intra-cellular delivery of reactive oxygen species (ROS) and heat, we designed a multifunctional nanoplatform to release ROS and heat directly in the cell nucleus for enhancing combined photodynamic therapy (PDT) and photothermal therapy (PTT) of tumors. As a photothermal agent, WS 2 nanoparticles were adsorbed photosensitive Au 25 (Captopril) 18 − (Au 25 ) nanoclusters via electrostatic interaction. And Dexamethasone (Dex), a glucocorticoid with nucleus targeting capability, played a key role in the intra-nuclear process of heat and ROS. PTT can increase intra-tumoral blood flow to promote Au 25 produce more ROS for PDT. Under near infrared (NIR) laser irradiation at a single 808 nm, these nucleus targeting WS 2 nanoplatforms showed a significant decreased cell viability of 18.2 ± 1.7% and a high DNA damage degree of 59.6 ± 8.3%. Furthermore, the WS 2 nanoplatform could be further used for X-ray computed tomography (CT) images. Taken together, our study provided a new prospect for effectively diagnostic and enhancing PTT/PDT efficacy.
研究领域:
肿瘤学
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纳米医学
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生物医学工程
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影像医学
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高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
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2025
·
IF 6.8
Jungryun Kim,Chong Hu,Paramesh Jangili,Chu Tang,Fu Wang,Jong Seung Kim
Residual tumor cells that persist after chemotherapy, even in minimal quantities, often exhibit drug resistance and increased invasiveness, potentially leading to tumor metastasis and recurrence. This study introduces a novel reactive oxygen species (ROS)-responsive prodrug, Dex-Dox, designed to overcome multidrug resistance (MDR) in tumor cells. The prodrug is composed of the anti-inflammatory glucocorticoid dexamethasone (Dex) conjugated with doxorubicin (Dox), a widely used antitumor agent, through an oxidative stress-responsive linker. Our in vitro findings revealed that, while Dex alone did not exhibit antitumor activity, Dex-Dox significantly enhanced drug sensitivity, promoting apoptosis and inhibiting angiogenesis in drug-resistant cells. Furthermore, in vivo therapeutic evaluations and histological analyses demonstrated that Dex-Dox substantially reduced tumor volumes, especially in a Dox-resistant tumor mouse model, underscoring its potential as an effective strategy against MDR in cancer therapy.
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CARBOHYDRATE POLYMERS
·
2019
·
IF 6.044
Xiaoyue Xu,Liping Sun,Li Zhou,Yanju Cheng,Feng Cao
Chitosan oligosaccharide-valylvaline-stearic acid (CSO-VV-SA) nanomicelles were designed for topical ocular drug delivery, based on peptide transporter-1 (PepT-1) active targeting. Hydrogenated castor oil-40/octoxynol-40 (HCO-40/OC-40) mixed nanomicelles were also prepared according to Cequa, just approved by FDA. Both nanomicelles produced no significant cytotoxicity and difference in human corneal epithelial cells (HCEpiC) and human conjunctival epithelial cells (HConEpiC). The active transport of CSO-VV-SA nanomicelles by PepT-1 was illustrated in the inhibitory test. Ex vivo fluorescence images of frozen sections indicated that the nanomicelles entered the posterior segment mainly through conjunctival route. In vivo precorneal retention study suggested dexamethasone from both nanomicelles could be detected for more than 3 h in rabbit tears. In vivo distribution evaluation of rabbits’ eyes showed the delivering efficiency of CSO-VV-SA nanomicelles was not inferior to that of HCO-40/OC-40 mixed nanomicelles. These findings indicated that CSO-VV-SA nanomicelles could become promising candidates for further clinical application.
研究领域:
药剂学
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眼科医学
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生物材料
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高影响因子
JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART A-TOXIC/HAZARDOUS SUBSTANCES & ENVIRONMENTAL ENGINEERING
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2020
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IF 1.724
Yue Leng,Yonghai Sun,Wei Huang,Chengyu Lv,Jingyan Cui,Tiezhu Li,Yongjun Wang
This study was conducted to determine the endocrine-disrupting effects of phthalate esters (PAEs) on the glucocorticoid receptor (GR) signaling. Potential (anti)glucocorticoid activities of six typical PAEs including di (2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DINP), dibutyl phthalate (DBP), diisobutyl phthalate (DIBP), diethyl phthalate (DEP) and dimethyl phthalate (DMP) were evaluated on human GR using cell viability assessment, reporter gene expression analysis, mRNA analysis, and molecular docking and simulation. For all tested chemicals, co-treatment of DEHP and DINP with dexamethasone (DEX) exhibited a synergistic effect on GR transactivity in the reporter assays. Such co-treatment also synergistically enhanced DEX-induced upregulation of GR mediated gene (PEPCK, FAS and MKP-1) mRNA expression in HepG2 cells and A549 cells. Molecular docking and dynamics simulations showed that hydrophobic interactions may stabilize the binding between molecules and GR. In summary, DEHP and DINP may be involved in synergistic effects via human GR, which highlight the potential endocrine-disrupting activities of PAEs as contaminants.
研究领域:
毒理学
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分子生物学
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环境科学
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高影响因子
KOREAN JOURNAL OF INTERNAL MEDICINE
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2025
·Vol. 40
·期 1
·92
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IF 2.4
Mingli Su,Ying Wang,Zheng Yan,Jia Luo,Jie Yang,Hua Ye,Aiming Liu,Julin Yang
Background/Aims Dexamethasone (DEX) is a widely used exogenous therapeutic glucocorticoid in clinical settings. Its long-term use leads to many side effects. However, its effect on metabolic disorders in individuals on a high-fat diet (HFD) remains poorly understood. Methods In this study, HFD-fed mice were intraperitoneally injected with DEX 2.5 mg/kg/day for 30 days. Lipid metabolism, adipocyte proliferation, and inflammation were assayed using typical approaches. Results DEX increased the epididymal fat index and epididymal adipocyte size in HFD-fed mice. The number of epididymal adipocytes with diameters > 70 μm accounted for 0.5% of the cells in the control group, 30% of the cells in the DEX group, 19% of the cells in the HFD group, and 38% of all the cells in the D+H group. Adipocyte proliferation in the D+H group was inhibited by DEX treatment. Adipocyte enlargement in the D+H group was associated with increased the lipid accumulation but not the adipocyte proliferation. In contrast, the liver triglyceride and total cholesterol levels and their metabolism were downregulated by the same treatment, indicating the therapeutic potential of DEX for nonalcoholic fatty liver disease. Conclusions DEX synergizes with HFD to promote lipid deposition in adipose tissues. A high risk of obesity development in patients receiving HFD and DEX treatment is suggested.
研究领域:
药理学
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内分泌学
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营养学
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代谢学
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2025
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IF 5.6
Xue Wang,Lu Liu,Di Wu,Yuxin Hu,Hongzhuo Liu,Yizhou Sun,Guangqi Yan
Noninfectious uveitis (NIU) remains a significant cause of vision impairment, typically managed with glucocorticoids. However, current glucocorticoid implants present considerable side effects, including elevated intraocular pressure and cataracts. To overcome these limitations, we synthesized a novel prodrug, dexamethasone gallate (DG), which possesses the powerful anti-inflammatory ability of dexamethasone (DEX) and exhibits strong antioxidant activity of gallic acid (GA) that helps protect ocular tissues against oxidative stress. DG was formulated into cyclodextrin microparticle suspension eye drops, designed to progressively disintegrate and penetrate ocular tissues effectively. In experimental autoimmune uveitis (EAU) models, DG suspension eye drops demonstrated comparable therapeutic efficacy to conventional DEX eye drops at reduced dosages, significantly reducing anterior and posterior ocular inflammation. Notably, DG formulations substantially minimized intraocular pressure elevation and glucocorticoid-related adverse effects. These findings support the potential of DG suspension eye drops as a safer, efficient, and patient-friendly therapeutic alternative for treating NIU.
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Journal of Materials Chemistry B
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2026
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IF 6.2
Tianyuan Zhang,Bingyu Cai,Fengyuan Zhang,Min Wang
This study developed a microfluidic-based method for the fabrication of dexamethasone-loaded silk fibroin microspheres (SFD), engineered for targeted pulmonary drug delivery. The microfluidic platform, combined with a self-assembly approach, enables green and simple synthesis of microspheres while allowing precise control over microsphere morphology, yielding a uniform aerodynamic diameter of 6.20 ± 0.14 μm and achieved high encapsulation efficiency of 74.46 ± 0.19% with a drug loading capacity of 17.18 ± 0.04%. Kinetic studies demonstrated sustained drug release for over 60 hours in phosphatebuffered saline (PBS), confirming the microspheres' potential for prolonged therapeutic action. While in vitro cytotoxicity assays showed slightly reduced A549 cell viability (<80%) due to dexamethasone's antiproliferative activity, the SFD exhibited minimal cytotoxicity (>95%) toward RAW264.7 macrophages. Furthermore, in a pro-inflammatory model, the SFD significantly suppressed secretion of key inflammatory cytokines including IL-1β, IL-6, and TNF-α, while minimizing systemic side effects through localized anti-inflammatory activity. This work addresses limitations of traditional pulmonary drug delivery systems by integrating microfluidic precision, controlled release, and targeted delivery into a biocompatible platform. By reducing off-target toxicity and enhancing therapeutic localization, the SFD system represents a transformative strategy for pulmonary inflammation treatment. The findings underscore the potential of microfluidic technologies to revolutionize precision medicine in respiratory therapeutics, with implications for clinical translation and personalized treatment protocols.
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TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2024
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IF 3.3
Yuhua Zuo,Chao Chen,Fasheng Liu,Hongmei Hu,Si Dong,Qinyuan Shen,Junquan Zeng,Ling Huang,Xinjun Liao,Zigang Cao,Zilin Zhong,Huiqiang Lu,Jianjun Chen
Background The global increase in the aging population has led to a higher incidence of osteoporosis among the elderly. Objective This study aimed to evaluate the protective properties of pinoresinol diglucoside (PDG), an active constituent of Eucommia ulmoides , against dexamethasone-induced osteoporosis and chondrodysplasia. Methods A zebrafish model of osteoporosis was established by exposing larval zebrafish to dexamethasone. The impact of PDG on bone mineralization was assessed through alizarin red and calcein staining. Alkaline phosphatase activity was quantified to evaluate osteoblast function. The influence of PDG on chondrogenesis was estimated using alcian blue staining. Fluorescence imaging and motor behavior analysis were employed to assess the protective effect of PDG on the structure and function of dexamethasone-induced skeletal teratogenesis. qPCR determined the expression of osteogenesis and Wnt signaling-related genes. Molecular docking was used to assess the potential interactions between PDG and Wnt receptors. Results PDG significantly increased bone mineralization and corrected spinal curvature and cartilage malformations in the zebrafish model. Furthermore, PDG enhanced swimming abilities compared to the model group. PDG mitigated dexamethasone-induced skeletal abnormalities in zebrafish by upregulating Wnt signaling, showing potential interaction with Wnt receptors FZD2 and FZD5. Conclusion PDG mitigates dexamethasone-induced osteoporosis and chondrodysplasia by promoting bone formation and activating Wnt signaling.
研究领域:
药理学
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生物学
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医学
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动物学
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分子生物学
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PubMed
高影响因子
Nanomaterials
·
2024
·Vol. 14
·期 7
·645
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IF 4.4
Yanqin Song,Pufan Yang,Wen Guo,Panpan Lu,Congying Huang,Zhiruo Cai,Xin Jiang,Gangqiang Yang,Yuan Du,Feng Zhao
Rheumatoid arthritis (RA) severely affects patients’ quality of life and is commonly treated with glucocorticosteroids injections, like dexamethasone, which may have side effects. This study aimed to create a novel low dose of twin-drug hydrogel containing dexamethasone and diclofenac and explore its potential as a drug delivery system for an enhanced anti-inflammatory effect. Its characterization involved rheology, transmission electron microscope (TEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Furthermore, the hydrogel demonstrated thixotropic properties. The hydrogel exhibited no cytotoxicity against RAW 264.7 macrophages. Furthermore, the hydrogel demonstrated a significant anti-inflammatory efficacy by effectively downregulating the levels of NO, TNF-α, and IL-6 in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. The co-delivery approach, when intra-articularly injected in adjuvant-induced arthritis (AIA) rats, significantly alleviated chronic inflammation leading to reduced synovitis, delayed bone erosion onset, and the downregulation of inflammatory cytokines. The biocompatibility and adverse effect evaluation indicated good biological safety. Furthermore, the hydrogel demonstrated efficacy in reducing NF-κB nuclear translocation in LPS-induced RAW 264.7 macrophages and inhibited p-NF-kB, COX-2, and iNOS expression both in RAW 264.7 macrophages and the joints of AIA rats. In conclusion, the findings indicate that the hydrogel possesses potent anti-inflammatory activity, which effectively addresses the limitations associated with free forms. It presents a promising therapeutic strategy for the management of RA.
研究领域:
药理学
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风湿病学
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材料科学
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生物医学工程
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ACS Nano
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2024
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IF 15.8
Wenjuan Ma,Junyi Che,Weiwei Chen,Dandan Wang,Huayong Zhang,Yuanjin Zhao
The therapeutic application of mesenchymal stem cells (MSCs) has good potential as a treatment strategy for systemic lupus erythematosus (SLE), but traditional MSC therapy still has limitations in effectively modulating immune cells. Herein, we present a promising strategy based on dexamethasone liposome-integrated MSCs (Dexlip-MSCs) for treating SLE via multiple immunomodulatory pathways. This therapeutic strategy prolonged the circulation time of dexamethasone liposomes in vivo, restrained CD4+T-cell proliferation, and inhibited the release of proinflammatory mediators (IFN-γ and TNF-α) by CD4+T cells. In addition, Dexlip-MSCs initiated cellular reprogramming by activating the glucocorticoid receptor (GR) signaling pathway to upregulate the expression of anti-inflammatory factors such as cysteine-rich secretory protein LCCL-containing domain 2 (CRISPLD2) and downregulate the expression of proinflammatory factors. In addition, Dexlip-MSCs synergistically increased the anti-inflammatory inhibitory effect of CD4+T cells through the release of dexamethasone liposomes or Dex-integrated MSC-derived exosomes (Dex-MSC-EXOs). Based on these synergistic biological effects, we demonstrated that Dexlip-MSCs alleviated disease progression in MRL/lpr mice more effectively than Dexlip or MSCs alone. These features indicate that our stem cell delivery strategy is a promising therapeutic approach for clinical SLE treatment.
研究领域:
免疫学
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干细胞治疗
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风湿病学
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PubMed
高影响因子
TALANTA
·
2024
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IF 5.6
Xuyuan Sun,Minmin Liu,Hao Liu,Li Li,Yaping Ding
In this work, a novel molecularly imprinted electrochemical aptasensor (MIEAS) was developed for highly selective detection of dexamethasone (Dex) in natural water environment. Gold nanoparticles (AuNPs) modified by nitrogen doped molybdenum carbide-graphene (N–Mo 2 C-Gr) were employed as the supports, where N–Mo 2 C-Gr improved the conductivity of the electrode and provided a larger specific surface area to polymerize more active substances. Using Dex as template molecule, o-phenylenediamine (o-PD) as the chemical functional monomer and aptamer as the biofunctional monomer, a molecularly imprinted polymer (MIP) membrane with Dex specific recognition sites was formed by electropolymerization. Due to the synergistic effect of MIP and aptamers, the as-prepared MIEAS exhibited a decent linear relationship to Dex detection within a relatively wide range of 10 −13 – 10 −5 M, and the detection limit was 1.79 × 10 −14 M. The recovery in actual water and tablet samples is satisfactory, which confirms the potential application prospects of this sensor in the determination of Dex.
研究领域:
分析化学
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环境科学
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纳米技术
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生物化学
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高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2018
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IF 2.559
Zhigang Nie,Sen Chen,Shuang Deng,Linsheng Long,Puji Peng,Mingyong Gao,Shile Cheng,Jiarui Cao,Hao Peng
Objective Glucocorticoids (GCs)-induced osteoblast apoptosis has been identified as an important cause of GCs related osteonecrosis of the femoral head (ONFH). Glycogen synthase kinase 3β (GSK3β) has been proved to mediate dexamethasone (Dex)-induced osteoblast apoptosis. This study aimed to investigate the underlying mechanism of GSK3β in Dex-induced osteoblast apoptosis. Methods Osteoblast cells were transfected with lentivirus expressing GSK3β-shRNA, and a DNA microarray was performed to analyze gene expression after Dex treatment with or without GSK3β-shRNA. Some differentially expressed genes were further validated by quantitative real-time-PCR (qRT-PCR). Results 460 genes were up-regulated (at least 2-fold) with Dex treatment but down-regulated (at least 2-fold) with GSK3β-shRNA treatment. In addition, 315 genes were down-regulated (at least 2-fold) with Dex treatment but up-regulated (at least 2-fold) with GSK3β-shRNA treatment. Among these genes, the apoptosis-related genes Hoxb8 , Kif18a , Dock8, Dlk1, Tnfsf14 , Casq2 , Bcl2l14 and mechanosensation-related gene Piezo2 were selected for further qRT-PCR analysis. 7 of 8 genes (Piezo2, Hoxb8, Kif18a, Dlk1, Tnfsf14, Casq2, Bcl2l14) showed the same tendency between gene chip results and qRT-PCR results. The microarray data also showed that apoptotic pathway, MAPK pathway, TGFβ pathway and Wnt pathway might be related to the mechanism of GSK3β in Dex-induced osteoblast apoptosis. Conclusion Our findings indicate that GSK3β-shRNA treatment can alter various genes expression levels and change diverse signaling pathways involved in Dex-induced osteoblast apoptosis. Furthermore, Piezo2, Hoxb8, Kif18a, Dlk1, Tnfsf14, Casq2 and Bcl2l14 genes may play an important role in the GSK3β-mediated osteoblast apoptosis process.
研究领域:
药理学
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细胞生物学
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分子生物学
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基因组学
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高影响因子
危险品化学品经营许可证（带存储）