JOURNAL OF NANOBIOTECHNOLOGY
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2018
·Vol. 16
·期 1
·1-10
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IF 5.294
Wang Shuai,Qu Fei,Han Wenli,You Jinmao
Background Differentiation of telomere length is of vital importance because telomere length is closely related with several deadly diseases such as cancer. Additionally, G-quadruplex and i-motif formation in telomeric DNA have been shown to act as a negative regulator of telomere elongation by telomerase in vivo and are considered as an attractive drug target for cancer chemotherapy. Results In this assay, Ag nanoclusters templated by hyperbranched polyethyleneimine (PEI–Ag NCs) are designed as a new novel resonance Rayleigh scattering (RRS) probe for sensitive differentiation of telomere length and monitoring special motifs (G-quadruplex and i-motif). In this assay, free PEI–Ag NC probe or DNA sequence alone emits low intensities of RRS, while the formation of PEI–Ag NCs/DNA complexes yields greatly enhanced RRS signals; however, when PEI–Ag NCs react with G-quadruplex or i-motif, the intensities of RRS exhibit slight changes. At the same concentration, the enhancement of RRS signal is directly proportional to the length of telomere, and the sensitivity of 64 bases is the highest with the linear range of 0.3–50 nM (limit of detection 0.12 nM). On the other hand, due to the conversion of telomere DNA molecules among multiple surrounding conditions, a DNA logic gate is developed on the basis of two chemical input signals (K + and H + ) and a change in RRS intensity as the output signal. Conclusion Our results indicate that PEI–Ag NCs can serve as a novel RRS probe to identify DNA length and monitor G-quadruplex/i-motif through the different increasing degrees of RRS intensity. Meanwhile, the novel attributes of the nanoprobe stand superior to those involving dyes or labeled DNA because of no chemical modification, low cost, green, and high efficiency.
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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PubMed
高影响因子
Journal of Analysis and Testing
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2022
·Vol. 6
·期 1
·12-19
·
IF 0
Wang Xin-Yan,Li Yuanfang,Lv Shuzhen,Bi Sai
Herein, a dual-signal electrochemical biosensor has been developed by self-assembly of pH-activatable i-motif probes on magnetic microparticles (MMPs) coupled with DNA walker for signal amplification. In this study, the cytosine (C)-rich single-stranded DNAs are hybridized with DNA initiators to obtain the long-nicked duplexes with repeated units, which are further captured on MMPs to form the magnetic i-motif containers. The resulting duplexes contain abundant G–C base pairs, thus providing extensive binding sites for doxorubicin (DOX). At acidic pH, the C-rich sequences are folded into i-motif structure, resulting in the release of DOX and walker initiators. In this case, the liberated DOX is adsorbed on graphene quantum dots-modified glassy carbon electrode via π–π interaction, while the walker initiators as a moving part can catalyze the hybridization between MB-modified fueler DNA and tracker DNA on electrode, contributing to the generation of dual electrochemical signals induced by MB and DOX. Importantly, the magnetic separation can effectively reduce the background, achieving sensitive biosensing of pH ranging from 4.0 to 7.4 with excellent stability. Moreover, the proposed dual-signal electrochemical biosensor has been successfully applied for accurate monitoring of pH in human serum, which holds great potential in pH-dependent bioassays, especially in ultra-micro analysis for clinical applications.
研究领域:
生物化学
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分析化学
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医学诊断
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DOI
ORGANIC & BIOMOLECULAR CHEMISTRY
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2018
·Vol. 16
·期 48
·9402-9408
·
IF 3.423
Pan Li,Zhe Chen,Yishun Huang,Jing Li,Fan Xiao,Shiyao Zhai,Zhiming Wang,Xuanjun Zhang,Leilei Tian
A new DNA-based fluorescent probe, which is a hybrid molecule of an i-motif forming sequence (IFS) and mono-functionalized tetraphenylethene (TPE), has been synthesized and investigated. A distinct pH-responsive aggregation-induced emission (AIE) effect has been observed from this hybrid molecule, i.e. the fluorescence of TPE will be turned on when the IFS part folds up under acidic conditions. According to the fact that a hybrid molecule with a relatively rigid structure shows a more obvious AIE effect, and whose nano-sized aggregates are formed at a high concentration, we assume that the solubility of the hybrid molecule in water will be reduced due to IFS folding, resulting in aggregation and the resultant AIE effect. Finally, due to its excellent pH responsiveness, this DNA-based probe employing an AIEgen has been applied in monitoring intracellular pH.
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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DOI
PubMed
高影响因子
TALANTA
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2016
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IF 4.035
Bei Hua Kang,Zhong Feng Gao,Na Li,Yan Shi,Nian Bing Li,Hong Qun Luo
Silver ions have been widely applied to many fields and have harmful effects on environments and human health. Herein, a label-free optical sensor for Ag + detection is constructed based on thiazole orange (TO) as a fluorescent probe for the recognition of i-motif DNA structure change at neutral pH. Ag + can fold a C-rich single stranded DNA sequence into i-motif DNA structure at neutral pH and that folding is reversible by chelation with cysteine (Cys). The DNA folding process can be indicated by the fluorescence change of TO, which is non-fluorescent in free molecule state and emits strong fluorescence after the incorporation with i-motif DNA. Thus, a rapid, sensitive, and selective method for the detection of Ag + and Cys is developed with a detection limit of 17 and 280 nM, respectively. It is worth noting that the mechanism underlying the increase of the fluorescence of thiazole orange in the presence of i-motif structure is explained. Moreover, a fluorescent DNA logic gate is successfully designed based on the Ag + /Cys-mediated reversible fluorescence changes. The proposed detection strategy is label-free and economical. In addition, this system shows a great promise for i-motif/TO complex to analyze Ag + in the real samples.
研究领域:
分析化学
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生物化学
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分子生物学
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环境科学
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DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
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2020
·
IF 4.321
Dandan Miao,Yanyan Yu,Yong Chen,Yin Liu,Gaoxing Su
Stimuli-responsive DNA-based nanostructures have emerged as promising vehicles for intelligent drug delivery. In this study, i-motif DNA-conjugated gold nanostars (GNSs) were fabricated in a facile manner as stimuli-responsive drug delivery systems (denoted as A-GNS/DNA/DOX) for the treatment of cancer via combined chemo-photothermal therapy. The i-motif DNA is sensitive to the environmental pH and can switch from a single-stranded structure to a C-tetrad (i-motif) structure as the environmental pH decreases from neutral (∼7.4) to acidic (<6.0). The loaded drug can then be released along with the conformational changes. To enhance cellular uptake and improve cancer cell selectivity, the aptamer AS1411, which recognizes nucleolins, was employed as a targeting moiety. The A-GNS/DNA/DOX nanocomposites were found to be highly capable of photothermal conversion and exhibited photostability under near-infrared (NIR) irradiation, and the pH and NIR irradiation effectively triggered the drug-release behaviors. In addition, the A-GNS/DNA/DOX nanocomposites exhibited good biocompatibility. The targeting recognition enabled the A-GNS/DNA/DOX to exhibit higher cellular uptake and therapeutic efficiency than the GNS/DNA/DOX. Notably, under NIR irradiation, a synergistic effect between chemotherapy and photothermal therapy can be achieved with the proposed delivery system, which exhibits much higher therapeutic efficiency both in monolayer cancer cells and tumor spheroids as compared with a single therapeutic method. This study highlights the potential of GNS/DNA nanoassemblies for intelligent anticancer drug delivery and combined cancer therapy.
研究领域:
纳米技术
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癌症研究
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药物递送系统
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生物医学工程
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2021
·
IF 9.229
Huihui Yang,Jun Chen,Yuling Liang,Yanfei Zhang,Wen Yin,Yuzhi Xu,Si-Yang Liu,Zong Dai,Xiaoyong Zou
Dynamic imaging of cell surface pH is extremely challenging due to the slight changes in pH and the fast diffusion of secreted acid to the extracellular environment. In this work, we construct a novel metal–organic framework (MOF)-shell-confined i-motif-based pH probe (MOFC-i) strategy that enables sensitive and dynamic imaging of cell surface pH. The CY3- and CY5-labeled i-motif, which is hybridized via its short complementary chain with two-base mismatches, is optimized for sensing at physiological pH. After efficiently anchoring the optimized pH probes onto the cell membrane with the aid of cholesterol groups, a biocompatible microporous MOF shell is then formed around the cell by cross-linking ZIF-8 nanoparticles via tannic acid. The microporous MOF shell can confine secreted acid without inhibiting the normal physiological activities of cells; thus, the MOFC-i strategy can be used to monitor dynamic changes in the cell surface pH of living cells. Furthermore, this method can not only clearly distinguish the different metabolic behaviors of cancer cells and normal cells but also reveal drug effects on the cell surface pH or metabolism, providing promising prospects in pH-related diagnostics and drug screening.
研究领域:
生物化学
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细胞生物学
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分子生物学
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生物医学工程
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DOI
PubMed
高影响因子
ACS Sensors
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2020
·
IF 7.333
Dandan Zhao,Haoran Tang,Hao Wang,Cheng Yang,Yongxin Li
The nanopore-based technique is a useful tool for single-molecule sensing and characterization. In this work, we have developed a new DNA-functionalized gold-modified nanopore, and analytes can induce the conformational switch of i-motif DNA formed on the inner surface of the nanopore. i-Motif DNA structure can be formed in the presence of silver ions (Ag+), which will result in the change in surface charge and structure of the nanopore tip and ion current rectification (ICR) ratio. The i-motif DNA structure on nanopore surface will be destroyed after the addition of glutathione (GSH) due to the strong interaction of Ag–S bond, which results in the recovery of surface charge, steric hindrance, and ICR ratio. This analyte-triggered conformational switch of i-motif DNA can help us deeply understand the DNA technology inside single nanopore and will benefit the possible applications in an ultrasensitive detection and biological/chemical analysis.
研究领域:
纳米技术
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生物物理学
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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
ANALYTICA CHIMICA ACTA
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2015
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IF 4.513
Zhong Feng Gao,Dong Mei Chen,Jing Lei Lei,Hong Qun Luo,Nian Bing Li
Improving the reproducibility of electrochemical signal remains a great challenge over the past decades. In this work, i-motif oligonucleotide probe-based electrochemical DNA (E-DNA) sensor is introduced for the first time as a regenerated sensing platform, which enhances the reproducibility of electrochemical signal, for label-free detection of glucose and urea. The addition of glucose or urea is able to activate glucose oxidase-catalyzed or urease-catalyzed reaction, inducing or destroying the formation of i-motif oligonucleotide probe. The conformational switch of oligonucleotide probe can be recorded by electrochemical impedance spectroscopy. Thus, the difference of electron transfer resistance is utilized for the quantitative determination of glucose and urea. We further demonstrate that the E-DNA sensor exhibits high selectivity , excellent stability, and remarkable regenerated ability. The human serum analysis indicates that this simple and regenerated strategy holds promising potential in future biosensing applications.
研究领域:
分析化学
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生物传感器
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电化学
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分子生物学
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DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2020
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IF 7.1
Xiangli Shao,Longjiao Zhu,Yangzi Zhang,Zaihui Du,Chunyan Sun,Wentao Xu
Molecular logic gates possess great potential for multi-parameter sensing, intelligent diagnostics, and molecular computation. One remaining challenge was to construct novel new logic gates based on smart nanomaterials and functional nucleic acids. In this study, two novel new logic devices were constructed utilizing ion-tuned DNA/copper nanoclusters (CuNCs), which were dual-responsive to K + and H + . By merely altering the arrangement of a specific sequence of the DNA stabilizer, two kinds of well-designed DNA probes permuted by G-tracts, C-tracts, and poly-T were designed as the building blocks of the logic device. Poly-T acted as the template for the formation of CuNCs. G-tracts and C-tracts enabled a K + /H + -responsive conformational switch into G-quadruplex (G4) and i-motif structures. Such a conformational conversion significantly modulated the fluorescence behaviors of CuNCs. This study discovered the unique interaction between the logic device and graphene oxide (GO). The logic devices were implemented for the analysis of K + and microRNA.
研究领域:
纳米技术
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生物化学
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分子生物学
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生物医学工程
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DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2021
·
IF 6.986
Li Li Li,Wen Yi Lv,Yao Wang,Yuan Fang Li,Chun Mei Li,Cheng Zhi Huang
DNA logic nanodevices have prospects in molecular recognitions but still face challenges in achieving DNA computation-controlled regulation in specific compartments of living cells. By incorporating the i-motif sequence and ATP aptamers into a Y-shaped DNA (Y-DNA) structure, and applying gold nanoparticles (AuNPs) as the transporting carrier, herein we present a new type of DNA logic nanodevices to monitor the ATP levels in lysosomes of living cells. Triple energy transfers including dual fluorescent resonance energy transfers (FRETs) and a nanometal surface energy transfer (NSET) occurred in the DNA logic nanodevices. It was identified that the proposed nanodevices perform an AND logic operation to output FRET signals only when an endogenous proton and ATP simultaneously exist in the cellular microenvironment. Owing to the use of the i-motif sequence, the nanodevices have lysosome-recognizing capacity without causing alkalization of the acidic organelle, making DNA computation-controlled regulation at the level of cellular organelles achievable. These DNA logic nanodevices show high application prospects in lysosome-related cellular function and disease treatment.
研究领域:
分子生物学
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纳米技术
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细胞生物学
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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
Acta Biomaterialia
·
2024
·
IF 9.4
Kunlin Li,Lin Li,Xiyue Xie,Jing Zhu,Daqing Xia,Lunli Xiang,Kaiyong Cai,Jixi Zhang
Although immunogenic cell death (ICD) induced by lysosomal membrane permeabilization (LMP) evidently enhance the effectiveness of antitumor immunity for triple-negative breast cancer (TNBC) with poor immunogenicity, their potential is increasingly restricted by the development of other death pathways and the repair of lysosomes by endoplasmic reticulum (ER) during LMP induction. Herein, a polydopamine nanocomposite with i-motif DNA modified and BNN6 loaded is prepared toward boosting LMP and immunotherapy of TNBC by synergy of spatially confined photoacoustic (PA) effects and nitric oxide. Combining the high-frequency pulsed laser (4000 kHz) with the intra-lysosomal assembly of nanocomposites produced spatially confined and significantly boosted PA effects (4.8-fold higher than the individually dispersed particles extracellular), suppressing damage to other cellular components and selectively reducing lysosomal integrity to 19.2%. Simultaneously, the releasing of nitric oxide inhibited the repair of lysosomes by ER stress, causing exacerbated LMP. Consequently, efficient immune activation was achieved, including the abundant releasing of CRT/HMGB1 (5.93–6.8-fold), the increasing maturation of dendritic cells (3.41-fold), and the fostered recruitment of CD4 + /CD8 + T cells (3.99–3.78-fold) in vivo. The study paves a new avenue for the rational design and synergy of confined energy conversion and responsive nanostructures to achieve the treatment of low immunogenicity tumors. Statement of Significance A strategy of boosting lysosomal membrane permeabilization (LMP) and concomitantly preventing the repair was developed to address the immunotherapy challenge of triple-negative breast cancer. Spatially confined and significantly enhanced photoacoustic (PA) effects were achieved through DNA-guided pH-responsive assembly of polydopamine nanocomposites in lysosomes and application of a high-frequency pulsed laser. Efficient immunogenic cell death was guaranteed by selective and powerful damage of lysosomal membranes through the significant contrast of PA intensities for dispersed/assembled particles and nitric oxide release induced endoplasmic reticulum stress. The study paves a new avenue for the rational design and synergy of confined energy conversion and responsive nanostructures to achieve the treatment of low immunogenicity tumors.
研究领域:
癌症生物学
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纳米技术
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免疫治疗
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生物医学工程
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光声成像
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Xiangshu Cheng,Ping Zhou,Changmei Chen,Fengyuan Liu,Lulu Wang,Rongchun Yi,Chao Yu,Tao Deng
Carbon dots (CDs) have been extensively studied in tumor therapy due to their excellent compatibility, remarkable stability, and luminescent properties. However, CDs-based therapeutic agents often face limitations such as rapid clearance, poor targeting, and weak responsiveness, which hinder their efficacy in achieving precise tumor treatment. To address these challenges, this study presents the construction of a dual-targeting, dual-responsive drug delivery platform with hierarchical structures: MV-DNA-CDs@DOX. Firstly, methacrylic acid-coated o-phenylenediamine carbon dots were synthesized using methacrylic acid and o-phenylenediamine. This was then conjugated with an i-motif-containing DNA sequence to create DNA-CDs with a “yarn ball-like” secondary structure. The nano-particles preserved the acid-responsive nature of the sequence and introduced an additional photo-responsive characteristic, enhancing the nanocarrier’s ability to deliver drugs deeply into tumor tissues. Upon loading with DOX, the polymeric nanocarrier was subject to biomimetic treatment, endowing it with active tumor-targeting capabilities and improving the specific distribution of the drug within tumor sites. Therefore, the use of biocompatible and responsive DNA segments as crosslinkers to construct organic nanopolymer carriers in the preparation of anti-tumor nanomaterials holds promise in expanding the application of nanotechnology in the field of cancer treatment.
研究领域:
纳米技术
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癌症治疗
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药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子