Asian Journal of Pharmaceutical Sciences
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2024
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IF 10.7
Hechen Wang,Xudan Shen,Xinlan Zhu,Su Zeng,Sheng Cai
Hepatocellular carcinoma (HCC) shows the highest morbidity among liver cancers and accounts for a major factor inducing cancer-associated mortality globally. It is characterized by genetic mutations in hepatocytes, leading to uncontrolled cell growth and proliferation. Treatment options for HCC include surgery, chemotherapy, and immunotherapy. But chemotherapeutics, which focus on single-targeted drug therapy, are still associated with certain limitations and may affect the treatment outcomes. Compared with chemotherapy drugs, natural products also show the anticancer effect of HCC and hypotoxicity, but overall low activity of natural products limits their further application. MiRNAs can modulate post-transcriptional functions of target genes. An increasing body of evidence has demonstrated that miRNAs are the key regulators in HCC by targeting different molecules in different signaling pathways. However, miRNAs are fragile and liable to catabolism by RNases in serum and other body fluids and small molecules separated from natural products may have limited bio-availability. According to this background, a chitosan based, targeted sustained-release nanoparticle delivery miR-128-3p agomir (NA-miR-128-3p) was developed in this work. This nanoparticle was prepared by pentasodium tripolyphosphate (TPP), chitosan hydrochloride, and miR-128-3p agomir with target aptamer which was loaded into the chitosan nanoparticle by self-assembly. It can intervene in HCC progress by affecting AKT1 expression. Based on this, a novel, efficient, long-acting, multi-mechanism, low-dosage combination drug delivery strategy was proposed in this work and showed a prominent anti-tumor effect. NA-miR-128-3p combined with natural product Oroxin B significantly affected HCC progression by the interference with VEGF and PI3K-AKT pathways, better than using NA-miR-128-3p and Oroxin B alone. Taken together, this nanoparticle and combinative administration compensate for the shortcomings of the fragile RNA drugs and the low activity of natural products, with high prospects in HCC treatment.
研究领域:
肿瘤学
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药学
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分子生物学
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纳米技术
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产品关联
DOI
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2022
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IF 10.753
Chenxi Zhao,Ruihui Xie,Qiuhui Qian,Jin Yan,Huili Wang,Xuedong Wang
As a broad-spectrum antibacterial agent, triclosan (TCS) has been confirmed to possess potential immunotoxicity to organisms, but the underlying mechanisms remains unclear. Herein, with the aid of transgenic zebrafish strains Tg ( coro 1A: EGFP) and Tg ( rag 2: DsRed), we intuitively observed acute TCS exposure caused the drastic differentiation, abnormal development and distribution of innate immune cells, as well as barriers to formation of adaptive immune T cells. These abnormalities implied occurrence of the cytokine storm, which was further evidenced by expression changes of immune-related genes, and functional biomarkers. Based on transcriptome deep sequencing, target gene prediction and dual luciferase validation, the highly conservative and up-regulated miR-19a was chosen as the research target. Under TCS exposure, miR-19a up-regulation triggered down-regulation of its target gene socs3b , and simultaneously activated the downstream IL-6/STAT3 signaling pathway. Artificial over-expression and knock-down of miR-19a was realized by microinjecting agomir and antagomir, respectively, in 1–2-cell embryos. The miR-19a up-regulation inhibited socs3b expression to activate IL-6/STAT3 pathway, and yielded abnormal changes in the functional cytokine biomarkers, along with the sharp activation of immune responses. These findings disclose the molecular mechanisms regarding TCS-induced immunotoxicity, and offer important theoretical guidance for healthy safety evaluation and disease early warning from TCS pollution.
研究领域:
毒理学
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分子生物学
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免疫学
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环境科学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2023
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IF 14
Yu Wang,Ye Wu,Bo Zhang,Cheng Zheng,Cheng Hu,Chuan Guo,Qingquan Kong,Yunbing Wang
Intervertebral disc degeneration (IDD) progresses due to local inflammatory response, gradually unbalanced anabolic/catabolic activity, and progressive functional impairment within the nucleus pulposus. Antagomir-21, a cholesterol-modified miRNA-21 inhibitor, has potential extracellular matrix (ECM) regenerative ability , but its application for IDD is limited by inadequate local delivery systems. An injectable hydrogel gene delivery system encapsulating a modified tannic acid nanoparticles (TA NPs) vector was engineered for on-demand and sustained delivery of antagomir-21 into the nucleus pulposus. After nucleus pulposus cell uptake, antagomir-21 was released from TA NPs and regulated the ECM metabolic balance by inhibiting the MAPK/ERK signaling pathway . TA NPs scavenged intracellular ROS and reduced inflammation by downregulating TNF-α expression. In vivo , synergistic anti-inflammatory effects and ECM regeneration effectively promoted therapeutic efficacy against IDD. This hydrogel gene delivery system represents a creative, promising strategy for IDD repair.
研究领域:
生物医学工程
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骨科
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基因治疗
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纳米技术
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再生医学
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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）