JOURNAL OF WUHAN UNIVERSITY OF TECHNOLOGY-MATERIALS SCIENCE EDITION
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2024
·Vol. 39
·期 4
·1048-1052
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IF 1.3
Yu Dan,Ye Liyuan,Li Binbin,Mou Fangzhi,Yin Yixia
pH-responsive charge reversal loaded miRNA nanocomposite was prepared by electrostatic self-assembly. The morphology, particle size and zeta potential of the nanocomposites were analyzed by transmission electron microscopy and dynamic light scattering. The synthesis of the polymer was analyzed by 1 H-NMR. The zeta-potential changes and cellular uptake effects of the nanocomplexes under different pH environments were investigated. The experimental results show that the surface morphology of the nanocomposite is spherical, and the average particle size is about 135 nm. As the pH value of the solution gradually decreases, the surface charge of the nanocomposite reverses from negative charge to positive charge (from −9.4 to +17.1 mV). Cellular uptake mediated by pH-responsive nanocomposite is selective for tumor cells, and the cellular uptake effect in tumor cells at pH 6.5 was approximately 3 times higher than that at pH 7.4. This pH responsive charge reversal nanocomposite has promising application prospects for gene delivery in the weak acid environment of tumors.
研究领域:
生物材料学
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分子生物学
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药物递送系统
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产品关联
DOI
高影响因子
ACS Nano
·
2024
·
IF 15.8
Xuantong Zhou,Fene Gao,Wenyan Gao,Qingzhen Wang,Xin Li,Xinyue Li,Wenxin Li,Jing Liu,Huige Zhou,Aiping Luo,Chunying Chen,Zhihua Liu
Despite the superior efficacy of radiotherapy in esophageal squamous cell carcinoma (ESCC), radioresistance by cancer stem cells (CSCs) leads to recurrence, metastasis, and treatment failure. Therefore, it is necessary to develop CSC-based therapies to enhance radiotherapy. miR-339-5p (miR339) is involved in stem cell division and DNA damage checkpoint signaling pathways based on ESCC cohort. miR339 inhibited ESCC cell stemness and enhanced radiation-induced DNA damage by targeting USP8, suggesting that it acts as a potential CSC regulator and radiosensitizer. Considering the limited circulating periods and poor tumor-targeting ability of miRNA, a multifunctional nanoplatform based on bismuth sulfide nanoflower (Bi@PP) is developed to efficiently deliver miR339 and improve radioresistance. Intriguingly, Bi@PP encapsulates more miR339 owing to their flower-shaped structure, delivering more than 1000-fold miR339 into cells, superior to free miR339 alone. Besides being used as a carrier, Bi@PP is advantageous for dynamically monitoring the distribution of delivered miR339 in vivo while simultaneously inhibiting tumor growth. Additionally, Bi@PP/miR339 can significantly enhance radiotherapy efficacy in patient-derived xenograft models. This multifunctional platform, incorporating higher miRNA loading capacity, pH responsiveness, hypoxia relief, and CT imaging, provides another method to promote radiosensitivity and optimize ESCC treatment.
研究领域:
肿瘤学
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分子生物学
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纳米技术
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放射生物学
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治疗学
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产品关联
DOI
PubMed
高影响因子
Materials Horizons
·
2025
·
IF 10.7
Linlin Zhao,Meiyu Hu,Xiaohang Yin,Hao Yang,Liyun Zhu,Pingyuan Sun,Xiya Wang,Songwei Ai,Yonghui Zheng,Genjie Li,Tingting Yang,Xuerui Chen,Jingyu Zhang
Effectively alleviating cerebral ischemia-reperfusion (I/R) injury is challenging despite medical advances. Prompt restoration of blood flow after ischemic stroke causes secondary damage to brain tissue, triggers neuroinflammation and overproduces reactive oxygen species (ROS). MiRNA regulates genes involved in neuron apoptosis and neuroinflammation, thus exhibiting potential in ameliorating cerebral I/R injury. However, as miRNA is vulnerable to degradation, its effective delivery poses obstacles to clinical applications. Inspired by therapeutic potential of miR-210 inhibitors in ischemic stroke-induced neuroinflammation, we constructed a multifunctional nanosystem composed of ceria nanozymes and zeolitic imidazolate framework-90 (ZIF-90) nanoparticles to deliver miR-210 inhibitors to treat cerebral I/R injury. Attributed to proton sponge effect of ZIF-90, this nanosystem allows for lysosome escape of miR-210 inhibitors to protect their intracellular bioactivity, while integration of ZIF-90 and ceria nanozymes utilizes multi-enzyme cascade activities to constrain lipid peroxidation and reduce oxidative damage in brain tissues of mice with middle cerebral artery occlusion (MCAO). After crossing the blood-brain barrier, miR-210 inhibitors target TET2 to suppress pro-inflammatory cytokines, finally inhibiting neuroinflammation. More than uncertain stability and efficacy of direct TET2 protein administration, delivery of miR-210 inhibitors by multifunctional nanosystems engendered neuroprotection, indicating their potential for protein replacement therapy against cerebral I/R injury.
研究领域:
神经科学
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纳米技术
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分子生物学
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药剂学
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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
Pharmaceutics
·
2023
·Vol. 15
·期 5
·1379
·
IF 5.4
Yongyu Tang,Ying Chen,Qianqian Guo,Lidan Zhang,Huanhuan Liu,Sibu Wang,Xingjie Wu,Xiangchun Shen,Ling Tao
Due to the accompaniment of vascular endothelial inflammation during the occurrence and development of cardiovascular diseases (CVD), treatment modalities against vascular endothelial inflammation have been intensively investigated for CVD prevention and/or treatment. Vascular cell adhesion molecule-1 (VCAM-1) is a typical transmembrane inflammatory protein specifically expressed by inflammatory vascular endothelial. By inhibiting VCAM-1 expression through the miR-126 mediated pathway, vascular endothelial inflammation can be efficiently relieved. Inspired by this, we developed a miR-126-loaded immunoliposome with VCAM-1 monoclonal antibody (VCAMab) decorated at its surface. This immunoliposome can be directly targeted to VCAM-1 at the inflammatory vascular endothelial membrane surface and achieve highly efficient treatment against inflammation response. The cellular experiment results showed the immunoliposome had a higher uptake rate towards inflammatory human vein endothelial cells (HUVECs) and can significantly downregulate the VCAM-1 expression level of inflammatory HUVECs. In vivo investigation further demonstrated that this immunoliposome displayed a higher accumulation rate at vascular inflammatory dysfunction sites than its non-VCAMab-modified counterpart. These results suggest that this novel nanoplatform can effectively deliver miR-126 to vascular inflammatory endothelium, opening a new avenue for the safe and effective delivery of miRNA for potential clinical application.Keywords:vascular endothelial inflammation treatment;miR-126 delivery;VCAM-1 targeting;cationic liposomes
研究领域:
心血管疾病
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纳米技术
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分子生物学
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药学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2023
·
IF 5.8
Shengnan Huang,Chengzhi Song,Jinxin Miao,Xiali Zhu,Yongyan Jia,Yafei Liu,Dongjun Fu,Benyi Li,Mingsan Miao,Shaofeng Duan,Zhenzhong Zhang,Yurong Hu
Dysregulation of microRNAs (miRNAs) expression is closely related to cancers and managing miRNA expression holds great promise for cancer therapy. However, their wide clinical application has been hampered by their poor stability, short half-life and non-specific biodistribution in vivo . Herein, a novel biomimetic platform designated as RHAuNCs-miRNA for improved miRNA delivery was prepared through wrapping miRNA-loaded functionalized Au nanocages (AuNCs) with red blood cell (RBC) membrane. RHAuNCs-miRNA not only successfully loaded miRNAs but also effectively protected them from enzymatic degradation. With good stability, RHAuNCs-miRNA had the characteristics of photothermal conversion and sustained release. Cellular uptake of RHAuNCs-miRNA by SMMC-7721 cells was in a time-dependent manner via clathrin- and caveolin-mediated endocytosis. The uptake of RHAuNCs-miRNAs was affected by cell types and improved by mild near infrared (NIR) laser irradiation. More importantly, RHAuNCs-miRNA exhibited a prolonged circulation time without the occurrence of accelerated blood clearance (ABC) in vivo, resulting in efficient delivery to tumor tissues. This study may demonstrate the great potential of RHAuNCs-miRNA for improved miRNAs delivery.
研究领域:
癌症生物学
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分子生物学
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纳米技术
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药学
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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）