Journal of Materials Chemistry B
·
2018
·Vol. 6
·期 15
·2217-2229
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IF 4.776
Shengnan Huang,Ying Liu,Xin Xu,Mengfei Ji,Yuanmin Li,Chengjun Song,Shaofeng Duan,Yurong Hu
A combination of different therapy strategies has great potential to efficaciously treat malignant tumors, by virtue of their synergetic effects. Herein, a co-delivery system based on gold nanocages (AuNCs) was designed to deliver both doxorubicin (DOX) and microRNA-122 mimic (miR-122) for an enhanced cancer therapy. DOX was loaded into the AuNCs and miR-122 was condensed onto the surface of the functionalized AuNCs by an electrostatic interaction. Polyethyleneglycol (PEG) and hyaluronic acid (HA) were also introduced to the co-delivery system for targeted drug delivery. We evaluated the cellular uptake, biodistribution and anti-tumor effect in vitro and in vivo. Our results demonstrated an effective delivery of DOX and miR-122 into tumor cells and the tumor tissue. Importantly, the triple therapy, namely the combination of chemotherapy, gene therapy and photothermal therapy, mediated by this multifunctional drug delivery system, exhibited better anti-tumor effect than any single therapy, both in vitro and in vivo. Additionally, this drug delivery system caused insignificant toxicity to the major organs and had no obvious effect on the body weight of the mice. It could be concluded that multifunctional AuNCs are promising as a co-delivery vector for an enhanced anti-tumor effect.
研究领域:
肿瘤学
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纳米医学
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基因治疗
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产品关联
DOI
PubMed
高影响因子
TALANTA
·
2017
·
IF 4.162
Sifang Lv,Feng Chen,Chunyan Chen,Xiaoming Chen,Hang Gong,Changqun Cai
We report a rapid and facile resonance light scattering (RLS) technique that utilizes CdTe quantum dots (CdTe QDs) probe to detect microRNA-122. The RLS sensor is ingeniously designed with P1 and P2 , two cDNA sequence probes with partially complementary sequences to miRNA-122. The amine-modified P1 and P2 are coupled to the surface of QDs to form functional QDs-P1 and QDs-P2 conjugates, which are collectively referred to as QDs-P. The cDNAs hybridize with the target miRNA to rapidly induce the self-assembly of QDs probe and change RLS intensity. The proposed technique can detect miRNA-122 within 40 min. RLS intensity is enhanced in proportion with miRNA-122 concentrations of 0.16–4.80 nM and has a low detection limit of 9.4 pM. In addition, the assay satisfactorily detects miRNAs in human serum samples. Thus, the assay has considerable potential for the analysis of other interesting tumor makers.
研究领域:
生物化学
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分子生物学
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分析化学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Wenli Zhang,Yuting Luo,Junke Tao,Geng Liu,Bei Li,Yu Teng,Jianrong Xu,Lei Feng,Zhen You
Designing a non-invasive, portable, and ultrasensitive detection strategy is crucial for the clinical point-of-care diagnosis of liver cancer, particularly given the low abundance of liver cancer biomarkers in complex fluid samples. Field-effect transistors provide an efficient detection method that can be miniaturized and integrated. Additionally, exosomal microRNAs in urine offer a promising approach for minimally invasive detection of biological fluids. However, developing a strategy that meets the requirements of portability, non-invasiveness, and ultra-sensitivity remains a significant challenge. In this study, an interdigitated field-effect transistor that incorporates metal carbide@carbon nanotubes (MC@CNT-iFETs) as the semiconductor material is introduced, specifically designed for the efficient detection of exosomal microRNA-122. The unique two-dimensional structure of the metal carbide significantly enhances sensitivity, while the inclusion of carbon nanotubes improves the electrical conductivity and transconductance of the semiconductor by 0.83-fold and 0.42-fold, respectively. The MC@CNT-iFETs demonstrate a limit of detection for microRNA-122, as low as 0.12 fM. Furthermore, these devices exhibit high specificity, reproducibility, and stability. Clinically, MC@CNT-iFETs demonstrates a strong correlation with q-PCR results, effectively distinguishing between 25 healthy individuals and 25 patients with liver cancer (R 2 = 0.8977). Statistical analyses reveal significant differentiation between controls and patients with liver cancer. Receiver operating characteristic curve analysis yields an area under the curve of 0.9776. These findings highlight the potential of MC@CNT-iFETs for ultra-sensitive, non-invasive detection of liver cancer in complex biofluids, particularly by providing ultrasensitivity, portability, and non-invasive diagnosis capabilities in personalized diagnostics and medicine.
研究领域:
医学诊断
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生物传感器
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纳米材料科学
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产品关联
DOI
高影响因子
Cell Reports Physical Science
·
2025
·
IF 7.3
Songbin Liu,Zhenghao Tao,Hongbing Liu,Shuang Yan,Longtianyang Lei,Yao Cheng,Runshu Fu,Haitao Zhang,Cui-Yun Yu,Hua Wei
The use of liver-specific endogenous microRNA-122 (miR-122) for efficient gene therapy of hepatocellular carcinoma (HCC) remains a significant challenge due to the severe immunosuppressive microenvironment of HCC. We report herein the construction of a miR-122-based cyclic brush spherical nucleic acid (SNA) nanoplatform for highly efficient gene therapy of HCC. Specifically, free miR-122 chains were conjugated to an optimized cyclic poly(2-hydroxyethyl methacrylate) (c-P(HEMA)) core via click chemistry, affording cyclic brush miR-122 (cb-P(HEMA-miR-122)), which can further self-assemble into stabilized SNAs with an ultra-small average hydrodynamic diameter of 105.8 nm. The resulting cb-P(HEMA-miR-122) SNAs can circumvent the immunosuppressive microenvironment of HCC and promote neutrophil polarization for activating the antitumor immunity, leading to a high tumor inhibition rate (TIR) of 87.4% in a Hepa1-6 mice HCC model. This study highlights the mere use of a cyclic topology for SNA construction as a robust yet simple strategy for enhanced gene-immunotherapy of HCC.
研究领域:
医学
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分子生物学
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肿瘤学
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免疫学
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DOI
高影响因子
Bioactive Materials
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2023
·
IF 18.9
Hongyan Wei,Fenfang Li,Tiantian Xue,Haixia Wang,Enguo Ju,Mingqiang Li,Yu Tao
As the most abundant liver-specific microRNA, microRNA-122 (miR122) played a crucial role in the differentiation of stem cells into hepatocytes. However, highly efficient miR122 delivery still confronts challenges including poor cellular uptake and easy biodegradation. Herein, we for the first time demonstrated that the tetrahedral DNA (TDN) nanoplatform had great potential in inducing the differentiation of human mesenchymal stem cells (hMSCs) into functional hepatocyte-like cells (HLCs) by transferring the liver-specific miR122 to hMSCs efficiently without any extrinsic factors. As compared with miR122, miR122-functionalized TDN (TDN-miR122) could significantly up-regulate the protein expression levels of mature hepatocyte markers and hepatocyte-specific marker genes in hMSCs, indicating that TDN-miR122 could particularly activate the hepatocyte-specific properties of hMSCs for developing cell-based therapies in vitro . The transcriptomic analysis further indicated the potential mechanism that TDN-miR122 assisted hMSCs differentiated into functional HLCs. The TDN-miR122-hMSCs exhibited hepatic cell morphology phenotype, significantly up-regulated specific hepatocyte genes and hepatic biofunctions in comparison with the undifferentiated MSCs. Preclinical in vivo transplantation appeared that TDN-miR122-hMSCs in combination with or without TDN could efficiently rescue acute liver failure injury through hepatocyte function supplement, anti-apoptosis, cellular proliferation promotion, and anti-inflammatory. Collectively, our findings may provide a new and facile approach for hepatic differentiation of hMSCs for acute liver failure therapy. Further large animal model explorations are needed to study their potential in clinical translation in the future.
研究领域:
分子生物学
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干细胞研究
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肝病
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纳米技术
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再生医学
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DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2020
·Vol. 187
·期 2
·1-9
·
IF 6.232
Xiang Ling,Zhang Feng,Feng Jian,Chen Chunyan,Cai Changqun
A method is described for the simultaneous determination of hepatocellular carcinoma-associated microRNA-122 and microRNA-199a/b-3p. This probe consists of two kinds of nanomaterials. The first comprises CdTe@CdS core-shell quantum dots which, on excitation at 375 nm give two emissions, with peak wavelengths at 543 (g-QDs) and at 627 nm (r-QDs). The second comprises gold nanoparticles acting as a quencher. In the absence of the target, g-QD-N1 and r-QD-N2 are stable due to the fluorescence stability. With the addition of microRNA-122 and microRNA-199a/b-3p, g-QD-N1 and r-QD-N2 are conjugated to the surface of AuNP-S1/S2 through base complementary pairing. As a result, fluorescence resonance energy transfer (FRET) occurs, resulting in a decrease at 550 nm and 635 nm respectively, which can realize the simultaneous detection of two different microRNAs. Detection is achieved within 50 min. The detection limits (3σ/k) are 0.2 nM for microRNA-122 and 0.5 nM for microRNA-199a/b-3p. The clinical applicability of the assay was demonstrated by detecting microRNAs in human serum and different cell lysates.
Schematic for the simultaneous determination of microRNA-122 and microRNA-199a/b-3p by FRET.
研究领域:
生物化学
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纳米技术
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癌症研究
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分子生物学
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产品关联
DOI
PubMed
高影响因子
METABOLIC BRAIN DISEASE
·
2021
·Vol. 36
·期 7
·2059-2069
·
IF 3.584
Yang Ling,Wang Lijuan,Wang Juan,Liu Ping
Long non-coding RNAs (lncRNAs) play important roles in ischaemic stroke. This study aimed to investigate the role and potential mechanism of lncRNA Gm11974 in ischaemic stroke. Mouse neuroblastoma N2a cells were treated with oxygen–glucose deprivation (OGD). The levels of Gm11974, microRNA-122-5p (miR-122-5p) and semaphorin 3A (SEMA3A) were detected by quantitative real-time PCR (qRT-PCR) or western blot. Cell viability and apoptosis were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, Caspase-3 Assay Kit and flow Cytometry. The levels of oxidative stress indicators were measured by using commercial kits. The relationship between miR-122-5p and Gm11974 or SEMA3A was verified by dual-luciferase reporter, RNA immunoprecipitation and RNA pull-down assays. Middle cerebral artery occlusion (MCAO) in mice was used to mimic ischaemic stroke. Gm11974 and SEMA3A were up-regulated, while miR-122-5p was down-regulated in OGD-treated N2a cells and MCAO mice. Down-regulation of Gm11974 ameliorated OGD-mediated N2a cell damage by increasing cell viability and reducing cell apoptosis and oxidative stress. Gm11974 promoted OGD-induced injury in N2a cells via negatively regulating miR-122-5p. Also, miR-122-5p alleviated OGD-resulted N2a cell injury by targeting SEMA3A. Moreover, silencing of Gm11974 decreased infarct volume and neurological score in MCAO mice. Knockdown of Gm11974 attenuated neuronal injury in ischaemic stroke by regulating miR-122-5p/SEMA3A signaling pathway.
研究领域:
神经科学
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分子生物学
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细胞生物学
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病理学
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产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2024
·
IF 18
Hongyan Wei,Tiantian Xue,Fenfang Li,Enguo Ju,Haixia Wang,Mingqiang Li,Yu Tao
The specific induction of hepatic differentiation presents a significant challenge in developing alternative liver cell sources and viable strategies for clinical therapy of acute liver failure (ALF). The past decade has witnessed the blossom of microRNAs in regenerative medicine. Herein, microRNA 122-functionalized tetrahedral framework nucleic acid (FNA-miR-122) has emerged as an unprecedented and potential platform for directing the hepatic differentiation of adipose-derived mesenchymal stem cells (ADMSCs), which offers a straightforward and cost-effective method for generating functional hepatocyte-like cells (FNA-miR-122-iHep). Additionally, we have successfully established a liver organoid synthesis strategy by optimizing the co-culture of FNA-miR-122-iHep with endothelial cells (HUVECs), resulting in functional Hep:HUE-liver spheroids. Transcriptome analysis not only uncovered the potential molecular mechanisms through which miR-122 influences hepatic differentiation in ADMSCs, but also clarified that Hep:HUE-liver spheroids could further facilitate hepatocyte maturation and improved tissue-specific functions, which may provide new hints to be used to develop a hepatic organoid platform. Notably, compared to transplanted ADMSCs and Hep-liver spheroid, respectively, both FNA-miR-122-iHep-based single cell therapy and Hep:HUE-liver spheroid-based therapy showed high efficacy in treating ALF in vivo. Collectively, this research establishes a robust system using microRNA to induce ADMSCs into functional hepatocyte-like cells and to generate hepatic organoids in vitro, promising a highly efficient therapeutic approach for ALF.
研究领域:
再生医学
·
分子生物学
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干细胞生物学
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肝病学
·
组织工程
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DOI
PubMed
高影响因子
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