JOURNAL OF NANOBIOTECHNOLOGY
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2024
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IF 10.6
Jinfeng Shi,Jiahui Zhou,Bo Liu,Kezhou Lin,Xingliang Xie,Xue Han,Yanmei Sheng,Yihan Liu,Congjian He,Yujin Zhou,Nan Zhu,Qian Yang,Ruifeng Luo,Yi Li
Background The oral administration of drugs for treating ulcerative colitis (UC) is hindered by several factors, including inadequate gastrointestinal stability, insufficient accumulation in colonic lesions, and uncontrolled drug release. Methods A multiple sensitive nano-delivery system comprising β-cyclodextrin (CD) and 4-(hydroxymethyl)phenylboronic acid (PAPE) with enzyme/reactive oxygen species (ROS) sensitivity was developed to load celastrol (Cel) as a comprehensive treatment for UC. Results Owing to the positive charge in the site of inflamed colonic mucosa, the negatively charged nanomedicine (Cel/NPs) could efficiently accumulate. Expectedly, Cel/NPs showed excellent localization ability to colon in vitro and in vivo tests. The elevated concentration of ROS and intestinal enzymes in the colon microenvironment quickly break the CD, resulting in Cel release partially to rebalance microbiota and recover the intestinal barrier. The accompanying cellular internalization of residual Cel/NPs, along with the high concentration of cellular ROS to trigger Cel burst release, could decrease the expression of inflammatory cytokines, inhibit colonic cell apoptosis, promote the macrophage polarization, scavenge ROS, and regulate the TLR4/NF-κB signaling pathway, which certified that Cel/NPs possessed a notably anti-UC therapy outcome. Conclusions We provide a promising strategy for addressing UC symptoms via an enzyme/ROS-sensitive oral platform capable of releasing drugs on demand. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1186/s12951-024-02725-9.
研究领域:
药学
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纳米技术
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胃肠病学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
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2017
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IF 6.402
Peng Li,XiaoYue Zhou,Ding Qu,Mengfei Guo,Chenyi Fan,Tong Zhou,Yang Ling
The aim of this study was to develop an amphipathic polyethylene glycol (PEG) derivative that was bi-terminally modified with celastrol and ginsenoside Rh2 (Celastrol-PEG-G Rh2). Such derivative was capable of forming novel, celastrol-loaded polymeric micelles (CG-M) for endo/lysosomal delivery and thereby synergistic treatment of lung cancer. Celastrol-PEG-G Rh2 with a yield of 55.6% was first synthesized and characterized. Its critical micellar concentration was 1 × 10−5 M, determined by pyrene entrapment method. CG-M had a small particle size of 121.53 ± 2.35 nm, a narrow polydispersity index of 0.214 ± 0.001 and a moderately negative zeta potential of –23.14 ± 3.15 mV. Celastrol and G Rh2 were rapidly released from CG-M under acidic and enzymatic conditions, but slowly released in normal physiological environments. In cellular studies, the internalization of celastrol and G Rh2 by human non-small cell lung cancer (A549) cells treated with CG-M was 5.8-fold and 1.8-fold higher than that of non-micelle control. Combinational therapy of celastrol and G Rh2 using CG-M exhibited synergistic anticancer activities in cell apoptosis and proliferation assays via rapid drug release within endo/lysosomes. Most importantly, the celastrol in CG-M exhibited a long elimination half-life of 445.3 ± 43.5 min and an improved area under the curve of 645060.8 ± 63640.7 ng/mL/h, that were 1.03-fold and 2.44-fold greater than those of non-micelle control, respectively. These findings suggest that CG-M is a promising vector for precisely releasing anticancer drugs within the tumor cells, and thereby exerts an improved synergistic anti-lung cancer effect.
研究领域:
药学
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肿瘤学
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纳米技术
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2021
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IF 8.128
Guijie Wei,Jianhua Chen,Ziqi Jing,Yanyi Li,Zhihui Li,Wei Zheng,Xiurui Sun,Wenwen Zhao,Zhe Zhang,Xue Wang,Hongcui Han,Chu Li,Yujie Zhang,Pengkai Ma
Mitochondria are appealing targets in cancer therapy for providing a suitable microenvironment and energy supply. Herein, we constructed a glycosylated poly(amido amine)/celastrol (PAMAM/Cel) complex for hypoxia-activated mitochondria-specific drug delivery and chemothermal therapy to inhibit tumor growth and metastasis. The complex was characterized by high photothermal conversion efficiency, hypoxia-sensitive polyethylene glycol (PEG) outer layer detachment, and alkaline-sensitive drug release. The complex showed specific cellular uptake in glucose transporter 1 (GLUT1)-overexpressing tumor cells and mitochondrial accumulation in a hypoxic environment. Combined with near-infrared (NIR) laser irradiation, the complex exhibited higher cytotoxicity, apoptosis induction, and metastasis inhibition rates due to the synergistic chemothermal effect. Similarly, the complex also targeted tumors and accumulated in mitochondria in tumor-bearing nude mice, resulting in superior inhibitory effects on tumor growth and metastasis as well as low systematic toxicity. Further mechanistic studies discovered that the complex impaired the mitochondrial membrane, reduced adenosine triphosphate (ATP) content, and regulated metastasis-related protein expression. Thus, the present study provides a promising nanomedicine for tumor therapy.
研究领域:
药学
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肿瘤学
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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
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Zihan He,Zhangwei Yang,Mingjie Hu,Kexing Wang,Zhenpeng Qiu,Qi Wang,Xinyan Chen,Cong Chang,Junjie Hu,Yan Meng
Celastrol (Cel) is a monomer from a famous traditional Chinese medicine named Tripterygium wilfordii Hook. f . Cel has shown great potential in treating intrahepatic cholangiocarcinoma (ICC) but still faces problems, including poor water solubility, high toxicity, and lack of targeting ability. Thus, the present work constructed a drug-delivery system using black fungus polysaccharide self-assembled -nanotubes (BFP). Cel-loaded nanotubes (BFP-Cel) were confirmed to have a high loading content of Cel (38 %), liver targeting, and enzyme-controlled release abilities. Moreover, BFP carriers could significantly increase the uptake efficiency of Cel by tumor cells. In vivo experiments showed that BFP-Cel could effectively inhibit tumor growth and reduce the physiological toxicity of Cel. Furthermore, BFP, as a carrier, could regulate the immune microenvironment in the liver through the activation of macrophages and play an immunomodulatory role. In summary, the BFP nanotube carrier could achieve detoxification and efficacy enhancement of Cel in treating ICC by increasing the targetability, controlled release ability, cell-uptake effect, and regulation of the immune microenvironment.
研究领域:
药理学
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肿瘤学
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纳米技术
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH BULLETIN
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2026
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IF 4.5
Yangchen Zheng,Pan Zhang,Qiuhua Xie,Fanfan Cao,Limin Xu
Post-stroke depression (PSD) is a common neuropsychiatric complication after stroke and is associated with impaired recovery and reduced quality of life. Increasing evidence suggests that neuroinflammation, serotonergic dysfunction, and synaptic impairment may all contribute to its pathophysiology. Celastrol, a bioactive compound with anti-inflammatory and neuroprotective properties, has shown potential therapeutic effects in several central nervous system disorders; however, its role in PSD remains insufficiently understood. In the present study, we investigated the effects of celastrol in a rat model of PSD induced by middle cerebral artery occlusion (MCAO) combined with chronic unpredictable mild stress (CUMS). Behavioral assessments showed that celastrol increased sucrose preference, reduced immobility time in the forced swim test, and improved exploratory activity in the open field test. Transcriptomic analysis of hippocampal tissue revealed enrichment of pathways related to inflammatory responses, neurotransmission, and synaptic function. Molecular analyses further showed that celastrol was associated with reduced microglial M1-related markers, increased expression of serotonergic-related proteins, and partial restoration of synaptic proteins, including postsynaptic density protein 95 and synapsin I. In addition, Golgi-Cox staining showed that celastrol treatment was accompanied by improved dendritic spine morphology in hippocampal CA1 pyramidal neurons. Together, these findings indicate that celastrol alleviated depressive-like behaviors in PSD rats and was associated with changes in neuroinflammatory, serotonergic, and synaptic markers. These results support further investigation of celastrol as a potential multi-target therapeutic candidate for PSD.
✓ 已验证
DOI
PubMed
高影响因子
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