ADVANCED FUNCTIONAL MATERIALS
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2018
·Vol. 28
·期 28
·1801118
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IF 13.325
Hai-Jun Liu,Xin Luan,Hai-Yi Feng,Xiao Dong,Si-Cong Yang,Zhong-Jian Chen,Qin-Yi Cai,Qin Lu,Yunpeng Zhang,Peng Sun,Mei Zhao,Hong-Zhuan Chen,Jonathan F. Lovell,Chao Fang
Mesoporous silica nanoparticles (MSN) can load and deliver potentially synergistic anticancer agents such as small molecule cytotoxics (like doxorubicin, DOX) and nucleic acids (like microRNA, miRNA). However, these cargos have different underlying chemical properties so overcoming respective intracellular delivery barriers is a key consideration. Strategies to deliver DOX from MSN frequently employ pH-driven mechanisms that are restricted to the acidic environment of lysosomes. Conversely, strategies to deliver miRNA make use of approaches that deliberately compromise lysosomal membrane integrity to enable cytosolic delivery of the payload. To reconcile these two needs (lysosomal delivery of DOX and intracellular delivery of miRNA), a new methodology by “weaving” polyethylenimine on the MSN surface through disulfide bonds to achieve superior delivery of chemotherapy (DOX) and miRNA therapy (using miRNA-145) is developed. Furthermore, an active targeting strategy based on a peptide ligand with affinity to glucose-regulated protein 78 (GRP78), a cell surface protein overexpressed in colorectal carcinoma, is developed. The active targeting approach results in enhanced synergistic antitumor effect both in vitro and in vivo in an orthotopic murine model of colorectal cancer. Taken together, this work demonstrates the capability and advantages of “smart” MSN delivery systems to deliver anticancer cargo appropriately to targeted cancer cells.
研究领域:
癌症研究
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纳米技术
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药学科学
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分子生物学
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高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2023
·
IF 8.4
Weidong Qin,Junhua Wang,Zhanqiu Tang,Hongyuan Tian,Zhenglong Wu
Quick and efficient immobilization of DNAs on gold nanoclusters (AuNCs) has a substantial impact on nanoscale applications relative to molecular recognition and patterned assembly. We found that in the presence of tris(2-carboxyethyl)phosphine (TCEP), chemisorption of thiolated DNA on the AuNC surface could be accomplished within 1.5 h, which was dramatically shorter than the incubation time needed in the conventional thiolate exchange reactions. Based on this observation, a core-shell-satellite nanocomposite consisting of magnetic nanoparticle , silica coating, and AuNCs (Fe 3 O 4 NPs@SiO 2 @AuNCs) was fabricated, on which a fluorescent hairpin probe was anchored with the assistance of TCEP. Integrated with duplex-specific nuclease (DSN)-assisted target recycling strategy, the sensing platform could simultaneously detect microRNA-21 and microRNA-141 with detection limits of 0.020 and 0.017 pM, respectively. The feasibility of the developed immobilization approach might significantly advance the use of DNAs and AuNCs in analytical sciences and clinical research.
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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.
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PubMed
高影响因子
Current Medical Science
·
2023
·Vol. 43
·期 2
·223-231
·
IF 2.4
Zhang Qing,Pan Rong-rong,Wu Yu-tao,Wei Yu-miao
Objective Vascular smooth muscle cell (VSMC) differentiation from stem cells is one source of the increasing number of VSMCs that are involved in vascular remodeling-related diseases such as hypertension, atherosclerosis, and restenosis. MicroRNA-146a (miR-146a) has been proven to be involved in cell proliferation, migration, and tumor metabolism. However, little is known about the functional role of miR-146a in VSMC differentiation from embryonic stem cells (ESCs). This study aimed to determine the role of miR-146a in VSMC differentiation from ESCs. Methods Mouse ESCs were differentiated into VSMCs, and the cell extracts were analyzed by Western blotting and RT-qPCR. In addition, luciferase reporter assays using ESCs transfected with miR-146a/mimic and plasmids were performed. Finally, C57BL/6J female mice were injected with mimic or miR-146a-overexpressing ESCs, and immunohistochemistry, Western blotting, and RT-qPCR assays were carried out on tissue samples from these mice. Results miR-146a was significantly upregulated during VSMC differentiation, accompanied with the VSMC-specific marker genes smooth muscle-alpha-actin (SMαA), smooth muscle 22 (SM22), smooth muscle myosin heavy chain (SMMHC), and h1-calponin. Furthermore, overexpression of miR-146a enhanced the differentiation process in vitro and in vivo . Concurrently, the expression of Kruppel-like factor 4 (KLF4), predicted as one of the top targets of miR-146a, was sharply decreased in miR-146a-overexpressing ESCs. Importantly, inhibiting KLF4 expression enhanced the VSMC-specific gene expression induced by miR-146a overexpression in differentiating ESCs. In addition, miR-146a upregulated the mRNA expression levels and transcriptional activity of VSMC differentiation-related transcription factors, including serum response factor (SRF) and myocyte enhancer factor 2c (MEF-2c). Conclusion Our data support that miR-146a promotes ESC-VSMC differentiation through regulating KLF4 and modulating the transcription factor activity of VSMCs.
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高影响因子
Bioengineered
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2021
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IF 3.269
Bo Li,Xianyi Liu,Guogang Wu,Jiawen Liu,Shouliang Cai,Fuxin Wang,Chunyu Yang,Jisheng Liu
Colorectal cancer (CRC) is a global public health issue with increasing prevalence. MicroRNA-934 (miR-934) is a kind of non-coding RNA involved in the regulation of diverse cancers. Though previous researches have revealed part of association between miR-934 and CRC, the role of miR-934 in CRC pathogenesis has not been completely explored yet. In this study, we aim to investigate the effect of miR-934 on cell proliferation, migration, invasion and angiogenesis in CRC. Accordingly, miR-934 was found to be over-expressed in SW480 and HCT116 cells, two typical CRC cell lines. Meanwhile, miR-934 knockdown significantly inhibited cell proliferation and induced cell cycle arrest in SW480 and HCT116 cells. It was further validated that miR-934 knockdown displayed an inhibitory effect on cell migration and invasion in SW480 and HCT116 cells. Additionally, miR-934 deficiency markedly decreased VEGF expression in SW480 and HCT116 cells and suppressed capability of CRC cells to promote tube formation in vascular endothelial cells, which suggests the pro-angiogenesis role of miR-934 in vitro. Dual luciferase reporter assay further showed that miR-934 directly bound to B-cell translocation gene 2 (BTG2). BTG2 knockdown reversed the inhibitory effect of miR-934 silencing on cell proliferation, migration, invasion, and angiogenesis in SW480 and HCT116 cells. In summary, this study suggests that miR-934 facilitates CRC progression by targeting BTG2, and further highlights the role of miR-934 in pathogenesis of CRC.
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高影响因子
Bioengineered
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2021
·
IF 3.269
Shanzhi Wan,Zhimin Liu,Yang Chen,Zhitao Mai,Mingming Jiang,Qingguo Di,Baohua Sun
MicroRNA (miR)-140-3p has been proved to repress lung adenocarcinoma (LUAD), and our study aims to further evaluate the mechanism. Bioinformatic analyses were performed. The viability, proliferation, migration, invasion and angiogenesis of transfected LUAD cells were all determined via Cell Counting Kit-8, colony formation, Scratch, Transwell, and tube formation assays. The targeting relationship between miR-140-3p and thymidylate synthetase (TYMS) was confirmed by dual-luciferase reporter assay. Relative expressions of miR-140-3p, TYMS, epithelial-to-mesenchymal transition- (E-cadherin, N-cadherin, vimentin), angiogenesis- (vascular endothelial growth factor (VEGF)), and apoptosis-related factors (cleaved caspase-3, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax)) were quantified by quantitative real-time polymerase chain reaction or Western blot. TYMS was high-expressed yet miR-140-3p was low-expressed in LUAD cells. Upregulation of miR-140-3p inhibited TYMS expression, viability, colony formation, migration, invasion, and tube length within LUAD cells, while downregulation of miR-140-3p did oppositely. Silenced TYMS, the downstream target gene of miR-140-3p, reversed the effects of miR-140-3p downregulation on TYMS expression, cell viability, colony formation, migration, invasion, and tube length as well as the metastasis-, apoptosis- and angiogenesis-related proteins in LUAD cells. Upregulation of miR-140-3p inhibited the proliferation, migration, invasion and angiogenesis of LUAD cells via targeting TYMS.
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PubMed
高影响因子
MICROCHIMICA ACTA
·
2019
·Vol. 186
·期 9
·1-9
·
IF 5.479
Chen Dongli,Zhang Meng,Zhou Fenyue,Hai Hong,Li Jianping
An electrochemiluminescent (ECL) biosensor is described for the determination of the breast cancer biomarker microRNA. The method is based on the amplification via target cyclic regeneration through a system of hairpin DNA probes, primers, and Klenow fragment of DNA polymerases combined with CdTe quantum dots (QDs) and gold nanoparticles. The assay is performed by exploiting the luminescence properties of CdTe-QDs and K 2 S 2 O 8 as a co-reactive agent to increase the ECL signal. It was successfully applied to ECL-based detection of a 20-mer microRNA. The sensor has a linear response in the 0.1 fM to 0.2 pM microRNA concentration range and a detection limit as low as 33 aM. The assay has been applied to the determination of microRNA spiked in serum samples, and recoveries ranged from 94.4 to 100.5%.
A novel electroluminescence biosensor based on the amplification of target cyclic regeneration is described. It is achieved by using a system of hairpin DNA probes, primers, and Klenow fragment of DNA polymerases combined with CdTe QDs and Au NPs, and was successfully applied to microRNA detection.
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高影响因子
BIOSENSORS & BIOELECTRONICS
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2024
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IF 10.7
Yujing Liang,Yifei Wang,Mengdi Yu,Yuqian Jiang,Jinhua Shang,Xiaoqing Liu,Fuan Wang
Biomolecules play essential roles in regulating the orderly progression of biochemical reaction networks. DNA-based biocircuits supplement an attractive and ideal approach for the visual imaging of endogenous biomolecules, yet their sensing performance is commonly encumbered by the undesired signal leakage. To solve this issue, here we proposed a glutathione (GSH)-activated DNA circuit for achieving the spatio-selective microRNA imaging through the successive response of a GSH-specific activation procedure and a non-enzymatic catalytic signal amplification procedure. In this design, by incorporating a disulfide bond into the pre-sealed nucleic acid probe, the uncontrolled circuitry leakage could be effectively ameliorated. In target cancer cells with high-abundant GSH and miR-21, endogenous GSH recognized and cleaved the pre-installed disulfide bond within DNA probes, thereby restoring the activity of circuitry components. The miR-21 then catalyzed the specific operation of circuitry for generating an amplified readout signal. We demonstrate that this system not only enables the effective discriminations of various cell types, but also contributes to the exploration of the correlationship between GSH and miR-21. This on-site activated DNA circuit can be extended to the robust analysis and exploration of different biomolecular interactions, offering a reliable reference for the in-depth understanding of biochemical interaction networks.
研究领域:
生物化学
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分子生物学
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医学诊断
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PubMed
高影响因子
ANALYTICAL CHEMISTRY
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2020
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IF 6.785
Xiangdan Meng,Kai Zhang,Fan Yang,Wenhao Dai,Huiting Lu,Haifeng Dong,Xueji Zhang
MicroRNAs (miRNAs) are involved in the essential progresses of many diseases and have emerged as therapeutic and diagnostic biomarkers. The combination of miRNA aberrant expression and tumor microenvironment (TME) features holds great potential for precise tumor imaging diagnosis but has been minimally explored. Herein, we rationally design a DNA@Cu-MOF nanosystem containing copper metal–organic frameworks (Cu-MOF) and a DNAzyme-assisted signal amplification procedure for deregulated miRNA-related hypoxic tumor diagnosis. The nanoprobes comprising a signal strand block Cu-specific DNAzyme precursor and a substrate strand are assembled on the surface of the hypoxia-responsive Cu-MOF. Under TME characterized by hypoxia, the DNA@Cu-MOF nanosystem disassociates and accomplishes the release of abundant Cu2+, DNAzyme precursor, and substrate strand. Target aberrant miRNA displaces the signal strand to recover one fluorescence signal for detection. Importantly, it activates the Cu-specific DNAzyme amplification, which produces miRNA aberrant expression-dependent fluorescence signal for hypoxic tumor diagnosis. Both in vitro and in vivo experiments validate its good performance for tumor cell diagnosis. The hypoxia-driven and miRNA-binding-induced self-powered and temporal-spatial fluorescence imaging nanosystem not only provides a great tool for aberrant miRNA-related hypoxic tumor diagnosis but also is readily applied for the control and modulation of biological functions.
研究领域:
生物医学工程
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分子生物学
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纳米医学
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高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2023
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IF 9.9
Yi Jin,Wei Yu,Wenkai Zhang,Chen Wang,Yao Liu,Wei-En Yuan,Yun Feng
Gene delivery for non-small-cell lung cancer treatment has been a challenge due to low nucleic acid binding ability, cell-wall barrier, and high cytotoxicity. Cationic polymers, such as the traditional “golden standard” polyethyleneimine (PEI) 25 kDa have emerged as a promising carrier for non-coding RNA delivery. However, the high cytotoxicity associated with its high molecular weight has limited its application in gene delivery. To address this limitation, herein, we designed a novel delivery system using fluorine-modified polyethyleneimine (PEI) 1.8 kDa for microRNA-942-5p-sponges non-coding RNA delivery. Compared to PEI 25 kDa, this novel gene delivery system demonstrated an approximately six-fold enhancement in endocytosis capability and maintain a higher cell viability . In vivo studies also showed good biosafety and anti-tumor effects, attribute to the positive charge of PEI and the hydrophobic and oleophobic properties of the fluorine-modified group. This study provides an effective gene delivery system for non-small-cell lung cancer treatment.
研究领域:
癌症治疗
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基因递送
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药学
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生物医学工程
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PubMed
高影响因子
European Review for Medical and Pharmacological Sciences
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2018
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IF 2.387
X. Lv,C.-Y. Li,P. Han,X.-Y. Xu
OBJECTIVE: MicroRNAs are a class of small non-coding RNAs that be involved in the pathogenesis of non-small cell lung cancer (NSCLC). The purpose of this study was to evaluate the effects of miR-520a-3p in cell growth and metastasis.MATERIALS AND METHODS: The mimics and inhibitor of miR-520a-3p were used to identify the effects of miR-520a-3p on cell proliferation and apoptosis using methylthiazol tetrazolium (MTT) assay and flow-cytometric method, respectively. Transwell assay was used to evaluate the cell migration and invasion. The protein expression levels related PI3K/AKT/mTOR signaling pathways were measured by Western blot.RESULTS: The results showed that miR-520a-3p overexpression could significantly inhibit cell proliferation and induce apoptosis, suppress cell migration and invasion. MiR-520a-3p overexpression could markedly reduce the ratio of p-AKT/AKT, p-PI3K/PI3K and Bcl-2/Bax, the levels of mTOR, matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) compared with control. However, miR-520a-3p overexpression could increase caspase-3 expression compared with control group. After inhibited the expression of miR-520a-3p, the capacity of cell proliferation, migration and invasion were increased, cell apoptosis was inhibited compared with control group. The ratio of p-AKT/AKT, p-PI3K/PI3K and Bcl-2/Bax, the levels of mTOR, MMP-2 and MMP-9 were increased compared with control group.CONCLUSIONS: Our study suggested that miR-520a-3p could suppress the NSCLC proliferation, migration and invasion through PI3K/AKT/mTOR signaling pathway.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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PubMed
高影响因子
NANO
·
2026
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IF 1.3
Wei Wei,Chenjie Tao,Yingying Zhou,Yongbin Meng,Peining Yan
Background: Cholangiocarcinoma (CCA) is an aggressive malignancy with poor prognosis, underscoring the need for novel diagnostic and therapeutic strategies. MicroRNAs (miRNAs) hold therapeutic promise but face delivery challenges. This study aimed to develop folic acid (FA)-targeted superparamagnetic albumin nanoparticles for miRNA delivery (FA-SAN-miRNA) and evaluate their potential for theranostic applications in CCA. Method: FA-SAN-miRNA was synthesized and characterized for size, zeta potential, morphology, magnetic properties, encapsulation efficiency, and drug release. In vitro studies assessed cytotoxicity, cellular uptake, proliferation inhibition in CCA cells (RBE, HuCCT1), and MRI contrast efficacy. In vivo targeting and tracking capabilities were evaluated in a CCA xenograft mouse model. Results: The synthesized FA-SAN-miRNA nanoparticles were spherical, well-dispersed, and superparamagnetic, with a size of 236.25 ± 4.31 nm and a zeta potential of 30.73 ± 5.82 mV. They exhibited high miRNA encapsulation efficiency (88.12 ± 4.63%) and a pH-responsive sustained release profile. FA-SAN-miRNA demonstrated low cytotoxicity, enhanced cellular uptake, and significant inhibition of CCA cell proliferation compared to non-targeted controls. The nanoparticles served as effective T2 contrast agents for MRI. In vivo, FA-SAN-miRNA identifying tumor cells with capture efficiency correlating with tumor burden. Conclusion: The FA-SAN-miRNA platform successfully integrates targeted miRNA delivery, pH-responsive release, and MRI capability, demonstrating potential for identifying tumor cells and targeted delivery in CCA. This multifunctional nanoplatform offers a promising strategy for improving CCA management.
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