ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Yexin Hu,Yuqing Cui,Zhemeng Zhang,Xinyi Zhang,Xiao Ma,Zhou Qiao,Feng Zheng,Feng Feng,Wenyuan Liu,Lingfei Han
Lipid nanoparticles (LNPs) are emerging as one of the most promising drug delivery systems. The long-circulating effect of intact LNPs (i-LNPs) is the key to efficacy and toxicity in vivo. However, the significant challenge is specific and sensitive detection of i-LNPs. Herein, a dual-recognition fluorescence enzyme-linked immunosorbent assay (DR-FELISA) was developed to directly isolate and detect i-LNPs by combining dual-recognition separation with a one-step signal amplification strategy. The microplates captured and enriched i-LNPs through antibody–antigen reaction. Dual-chol probes were spontaneously introduced into the lipid bilayer of captured i-LNPs, converting the detection of i-LNPs into the detection of double-cholesterol probes. Finally, the end of the dual-chol probes initiated the localized scaffolding autocatalytic DNA circuits (SADC) system for further signal amplification. The SADC system provides a sensitive and efficient amplifier through localized network structures and self-assembled triggers. Simultaneous recognition of i-LNPs surface PEG-lipid and lipid bilayer structures significantly eliminates interference from biological samples. i-LNPs were detected with high selectivity, ranging from 0.2 to 1.25 mg/mL with a limit of detection of 0.1 mg/mL. Moreover, this method allows the isolation and quantitative analysis of different formulations of i-LNPs in serum samples with a satisfactory recovery rate ranging from 94.8 to 116.3%. Thus, the DR-FELISA method provides an advanced platform for the exclusive and sensitive detection of i-LNPs, providing new insights for the study of the quality and intracorporal process of complex formulations.
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MICROCHIMICA ACTA
·
2017
·Vol. 184
·期 10
·4021-4027
·
IF 4.58
Wang Xiaole,Niazi Sobia,Yukun Huang,Sun Weijia,Wu Shijia,Duan Nuo,Hun Xu,Wang Zhouping
The authors describe an aptasensor based on time-resolved fluorescence resonance energy transfer (TR-FRET) for the identification of Salmonella typhimurium ( S. typhimurium ). Aptamer-functionalized nanoparticles (NPs) is used as the energy donor, and a complementary oligonucleotide (cDNA) labeled with carboxyfluorescein (FAM) acts as the acceptor. The detection scheme is based on the hybridization between aptamer and cDNA, upon which photonic energy is transferred from NPs to FAM unless aptamer interacts with S. typhimurium . Due to the highly specific recognition ability of aptamer and the strong fluorescence intensity of NPs, the method is highly sensitive and selective for S. typhimurium . Under the optimal conditions, at excitation wavelength of 273 nm, a delay time of 100 μs and a gating time of 1 ms, the integrated time-resolved fluorescence intensity ratio (FAM 520 /Tb 489 ) is linear in the 100 to 10 6 cfu·mL −1 range, and the limit of detection is as low as 25 cfu·mL −1 . The assay was applied to the analysis of eggs and chicken meat for S. typhimurium , and the results were consistent with those of a plate-counting method.
Schematic of a homogeneous time-resolved FRET assay for the determination of Salmonella typhimurium by FRET between NaYF 4 :Ce/Tb nanoparticle-tagged aptamer and FAM-cDNA, with a good linearity and the limit of detection of 25 cfu mL −1 .
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Advanced Science
·
2025
·
IF 14.1
Jizhuo Li,Wenze Xun,Xijie Wang,Ruiguang Luo,Qifan Hu,Zhaocai Zhou,Jian Yuan,Yanan Wang,Xiaorui Wan,Tao Zhao,Tianyu Han,Jian-Bin Wang
Lactylation is a novel post-translational modification closely related to the glycolytic process, but the regulatory mechanisms between lactylation and glycolysis are far from being elucidated. Lactate dehydrogenase A (LDHA) catalyzes the formation of lactate, which provides the modifying group for protein lactylation. However, whether lactylation occurs on LDHA itself remains unknown. Here, it is found that lactylation promotes the enzymatic activity of LDHA in lung adenocarcinoma (LUAD), which in turn enhances the overall level of cellular lactylation through a positive feedback loop. Screening identified Lys81 and Lys318 as key LDHA lactylation sites, with alanyl-tRNA synthetase 1 (AARS1) serving as the mediating lactyltransferase. Mass spectrometry reveals that numerous proteins involved in DNA nonhomologous end junction (NHEJ), including FEN1, XRCC5, and XRCC6 might be regulated by lactylation. Delactylation of these proteins significantly hinders the formation of FEN1-RAD1-RAD9A-HUS1 complex, thereby leading to dysfunction of NHEJ and increasing the sensitivity of cancer cells to cisplatin. In summary, this work identifies LDHA lactylation as a critical mechanism for accelerating the progression of LUAD and reveals how this lactylation influenced cisplatin sensitivity of LUAD cells, which deepen the understanding of lactylation-mediated tumor progression and provide a potential new anticancer strategy.
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CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
LuLu Cao,Xianqiang Gao,Yunlei Zhou,Shugang Zhang,Miao Zhang,Huanshun Yin
The advanced structural design of semiconductor photoactive materials is the core element to improve the performance of photoelectrochemical (PEC) biosensors. By constructing a BiOIO 3 @Bi 4 O 5 Br 2 Z-Scheme heterojunction with abundant oxygen vacancies to significantly improve the photoelectric conversion efficiency, a sensitively PEC biosensor for MBD2 detection was designed by combining DNA isothermal cycle double amplification technology. Specifically, the chitosan-modified BiOIO 3 @Bi 4 O 5 Br 2 was modified on the surface of ITO electrode. Methylene blue (MB)-DNA was immobilized on due to the covalent reaction of its carboxyl group with the amino group of chitosan, and the excess amino group was blocked with acetaldehyde. In the absence of MBD2, the cleavage activity of HpaII is inhibited due to the retention of cytosine methylation. which triggers ISDPR and large amounts of single-stranded DNA complementary to MB-DNA was produced. After MB-DNA hybridization, Exo III was triggered to assist the MB-DNA hydrolysis cycle, resulting in the drop of MB, causing a decrease in the photoelectric signal. Conversely, in the presence of MBD2, it removed cytosine methylation, triggering HpaII hydrolysis and inhibiting subsequent reactions, so that the MB connected to the electrode is retained and the photoelectric signal is enhanced. The sensor had a detection range from 0.07 to 500 ng/mL with a detection limit of 0.018 ng/mL (3σ). The study also explores the effects of environmental pollutants on MBD2 activity and validated with molecular docking models, offering insights into epigenetic regulation and environmental health assessments. This work underscores the potential of advanced photoactive materials and heterojunction designs in biosensor applications.
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CHEMISTRY-A EUROPEAN JOURNAL
·
2014
·Vol. 21
·期 7
·2930-2935
·
IF 5.696
Li Zhou,Wei Li,Zhaowei Chen,Enguo Ju,Jinsong Ren,Xiaogang Qu
Graphical CuS-tom made : Facile growth of CuS nanowires through self-assembly and their application as building blocks for near-infrared light-responsive functional films is demonstrated (see figure). In vitro studies have shown that the hybrid film possessed excellent biocompatibility and the release rate of chemical molecules from the film could be controlled in a highly spatial and temporal precision. Facile growth of CuS nanowires through self-assembly and their application as building blocks for near-infrared light-responsive functional films have been demonstrated. It is found that DNA is a key factor in preparing the CuS material with defined nanostructure. An exclusive oriented self-aggregate growth mechanism is proposed for the growth of the nanowires, which might have important implications for preparing advanced, sophisticated nanostructures based on DNA nanotechnology. By employing the hydrophilic CuS nanowire as an optical absorber and thermosensitive nanogel as guest reservoir inside alginate film, a new platform for the release of functional molecules has been set up. In vitro studies have shown that the hybrid film possesses excellent biocompatibility and the release rate of chemical molecules from the film could be controlled with high spatial and temporal precision. Our novel approach and the resulting outstanding combination of properties may advance both the fields of DNA nanotechnology and light-responsive devices.
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TOXICOLOGY
·
2021
·
IF 4.221
Zixuan Liu,Qiushuang Zhu,Erqun Song,Yang Song
Polybrominated diphenyl ethers (PBDEs) are world-wide used flame retardants before they were listed as Persistent Organic Pollutants (POPs) by the Stockholm Convention. Previously, our studies indicated that a quinone type of PBDE metabolite (PBDEQ) exposure was linked with neurotoxicity via excess free radical formation and oxidative stress. However, it is current unknown the effect of PBDEQ on genetic biomacromolecules DNA and corresponding biological consequences in neurological cells. Here, by employing phosphorylated histone H2AX in Serine 139 (γ-H2AX) and comet assay in microglia BV2 cells, our data suggested PBDEQ could triggered DNA damage. Furthermore, PBDEQ exposure led to the caspase 3-dependent cell apoptosis. Moreover, PBDEQ induced G2/M-phase cell arrest in a p53-dependent manner. Notably, p53 activation coordinated cell cycle progression, alleviated DNA damage and ultimately mitigated apoptosis in BV2 cells. Finally, antioxidant N -acetyl- l -cysteine (NAC) inhibited p53 activation upon PBDEQ exposure, and then ameliorated PBDEQ-induced DNA damage, cell cycle arrest and apoptosis, which illustrated that PBDEQ-induced DNA damage and p53 activation were mediated by reactive oxygen species (ROS). Together, the current findings unveil the fundamental toxicological mechanisms of PBDEQ, which propose a potential therapeutic strategy against the adverse effect caused by PBDE exposure.
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BIOCHEMICAL PHARMACOLOGY
·
2021
·
IF 5.858
Cen Zhao,Dawei Yang,Yuchen Ye,Zhenzhong Chen,Tifan Sun,Jiawei Zhao,Kai Zhao,Na Lu
Multiple myeloma (MM) is a malignancy of antibody-producing plasma cells with genomic instability and genetic abnormality as its two hallmarks. Therefore, DNA damage is pervasive in MM cells, which indicates irregular DNA damage response (DDR) pathway. In this study, we demonstrated that LT-171-861, a multiple kinase inhibitor , could inhibit proliferation and induce apoptosis in MM cells. LT-171-861 promoted DDR pathway and triggered DNA damage through impeding the process of homologous recombination in double strand breaks, rather than directly elevating ROS level in MM cells. Mechanism research revealed that Pim2 inhibition was responsible for LT-171-861-indcued DNA damage and cell apoptosis. LT-171-861 mainly suppressed Pim2 kinase activity and reduced the expression of its phosphorylated substrates, such as 4EBP1 and BAD. Moreover, Olaparib , a PARP inhibitor , could enhance the antitumor effect of LT-171-861 in suppressing tumor growth in MM xenografted nude mice . Taken together, our results demonstrated that LT-171-861 showed a promising therapeutic potential for MM and had an additional lethal effect with PARP inhibitors.
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SENSORS AND ACTUATORS B-CHEMICAL
·
2016
·
IF 4.758
Bingying Jiang,Fangzhen Li,Cuiyun Yang,Jiaqing Xie,Yun Xiang,Ruo Yuan
The construction of simple and highly sensitive aptasensors will significantly advance the monitoring of proteins. In this work, we have developed a convenient and label-free protein-induced catalytic hairpin assembly signal amplification approach for aptamer-based sensitive electrochemical detection of thrombin in human serums. The target thrombin binds the aptamer-containing hairpin probes immobilized on the sensor electrodes and triggers catalytic assembly of other two hairpins to form many G-quadruplex Y-junction DNA structures in situ . These G-quadruplex structures further associate with hemin to form G-quadruplex/hemin complexes, which are then subject to electrochemical measurement and generate substantially amplified current output for label-free and sensitive detection of thrombin. The developed aptasensor shows a dynamic range of 0.01–1.0 nM and a detection limit of 6.0 p.m for thrombin detection. The sensor can also discriminate the target thrombin against other non-target proteins and exhibits promising results for detecting thrombin in human serums. With the successful construction of the thrombin aptasensor, our signal amplified method can be potentially applied to detect other target molecules by choosing appropriate aptamer/ligand pairs.
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TALANTA
·
2019
·
IF 4.916
Tian Wu,Xiang Li,Yuanqi Fu,Xuelian Ding,Zhongjian Li,Guifen Zhu,Jing Fan
Developing the high selectivity and sensitivity strategy for nucleic acid detection is crucial for early diagnosis and therapy of diseases. In this work, a novel low back-ground fluorescent sensor platform for the detection of nucleic acid has been developed based on δ-FeOOH nanosheets integrating with exonuclease III-assisted target-recycling signal amplification. Because of the strong binding ability between the single-strand DNA (ssDNA) and the δ-FeOOH nanosheets, the dye-labeled ssDNA probe would be quenched by δ-FeOOH nanosheets through fluorescence resonance energy transfer (FRET). By using magnetic separate properties of δ-FeOOH, the background signal was separated from the sensor system, and the low background sensor system was obtained. After adding the target DNA, a double-strand DNA complex (dsDNA) would be formed between the target DNA and dye-labeled ssDNA probe. Then, the dye-labeled ssDNA probe in the dsDNA complex would be stepwise hydrolyzed into short fragments from 3′-terminus by Exonuclease III, and the fluorescence signal was recovered due to the weak bind affinity between the short fragments and δ-FeOOH nanosheets. By using the fluorescence quenching ability of δ-FeOOH nanosheets and enzyme-assisted target-recycling signal amplification, this strategy could show an excellent selectivity toward hepatitis C virus DNA with a low detection limit of 10 pM. By simply changing the dye-labeled ssDNA probe sequence, this sensing platform can be developed as a universal approach for the simple, sensitive, and selective detection of different target DNA.
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ANALYTICA CHIMICA ACTA
·
2021
·
IF 6.558
Kaicha Chen,Hongli Zhao,Zhenxing Wang,Minbo Lan
The detection of circulating tumor DNA (ctDNA) has increasingly received a great deal of attention considering its significance in cancer diagnosis. And the signal amplification plays an important role in the development of sensitive ctDNA biosensors . Herein, the nanocomposites (denoted as HAC-AuPt), integrating from high-active carbon (HAC) and AuPt alloy nanoparticles , were synthesized and subsequently used as a signal amplification label to fabricate a sandwich-type ctDNA electrochemical biosensor. Characterizations demonstrated that HAC presents uniform size distribution and AuPt alloy nanoparticles were successfully loaded on HAC. The current response could be amplified to a great extent by the resultant HAC-AuPt due to its excellent electrochemical property. The nanocomposites were further bounded with DNA signal probes (SPs) via Au-S or Pt-S assembly to form SPs-label. After the capture probes (CPs) were immobilized on the electrode surface, the target DNA (tDNA) and SPs-label were stepwise incubated on the CPs-modified electrode, thus forming a sandwich-type structure. By monitoring the catalytic signal of HAC-AuPt towards the reduction process of H 2 O 2 , this biosensor provided a wide linear range of 10 −8 mol/L - 10 −16 mol/L with a low detection limit of 3.6 × 10 −17 mol/L (S/N = 3) for the detection of the tDNA. Furthermore, obvious differences in response signals among different DNAs were observed benefitting from the excellent selectivity of the biosensor. Besides, the long-term stability, reproducibility, and recovery rate were proved to be outstanding. These results indicate that the established biosensor holds a potential application in the clinical diagnosis of ctDNA.
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SENSORS AND ACTUATORS B-CHEMICAL
·
2021
·
IF 7.46
Kai-Xin Song,Dong Chen,Zi-Yang Liao,Xuan Yu,Fei-Fei Guo,Ri-Lei Yu,Meng-Zhen Xu,Ya-Mu Xia,Wei-Wei Gao
In this work, an efficient electrochemical biosensor for the detection of DNA damage induced by the interaction of a novel antitumor agent AD-NU was investigated by CV , DPV and SWV methods. The GCE was modified with calf thymus DNA, G-quadruplexes, poly dA and poly dG, respectively. Among all the candidates, compound AD-NU was the optimum ligand because of the minimum energy when binding to DNA or TOP II by molecular docking. The electrochemical analysis revealed the redox mechanism of AD-NU on the GCE surface, which included two consecutive reversible processes of 9,10-diquinone and irreversible redox of nitroso group . The DNA damage caused by AD-NU was investigated by comparing the intensity changes of dGuo and dAdo oxidation peaks in DNA strands, and monitoring the appearance of peak for oxidative product 8-oxoGua. Further confirmation for the interaction between AD-NU and DNA was performed by UV–vis absorption and fluorescence titration, which implied the intercalation of AD-NU into DNA base pairs with a high affinity constant ( K b = 13.7 ×10 5 M −1 ). The electrophoresis also revealed the potency of AD-NU to cleave and unwind DNA strands. Finally, AD-NU was proved to have good antiproliferative activity toward tumor cells, with IC 50 values of 3.0 μmol ∙ L −1 for A549 cell lines and 3.3 μmol ∙ L −1 for Hela cell lines, superior to MTZ reference.
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JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2016
·
IF 3.169
Xiaoling Xu,Fang Gao,Xincai Xiao,Yan Hu,Chaozhen Zhu,Dan Zhao
The identification of spatial structures of drugs and the researches on their interaction mechanism with DNA are always attractive to the researchers. However, their realization is lack of simple and fast method. This paper reports the establishment of multiple-functional detection platform based on the “turn off-on” model of ZnCdSe quantum dots. In this system, ZnCdSe quantum dots work as the fluorescent probe, platinum anti-cancer drugs as the quencher and triplex DNA as the trapping agent. The seemingly similar cisplatin and transplatin exhibited different fluorescent recovery behaviors due to their difference in structure, and thus realized the selective detection of cisplatin and transplatin with the reaction time set at 10 min as well as the quantitation of cisplatin over the range of 2.5 × 10 −8 –100 × 10 −8 M. Based on this, the interactions between platinum anti-cancer drugs and ctDNA as well as polymorphic DNA were further studied, and realized the recognition of triplex DNA. The multiple-functional detection platform integrates the functions of the filtration of high-efficient platinum anti-cancer drugs, the researches on interaction mechanism of drugs, and the recognition of polymorphic DNA, meaningful to the future treatment of viral and cancers based on antisense gene strategy.
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