TALANTA
·
2018
·
IF 4.244
Qiao Liu,Xing-Li Xie,Chang-Jie Mao,Jing-Shuai Chen,He-Lin Niu,Ji-Ming Song
A highly selective DNA-based electrochemiluminescence (ECL) based biosensor is described for the detection of human IgG. It is exploiting the effect of steric hindrance that affects the strength of the ECL signal in the presence of IgG. Digoxin-linked signaling DNA was specifically bound to IgG, and this causes steric hindrance which limits the ability of DNA to hybridize with capturing DNA attached to a gold electrode. Europium (II) doped CdSe quantum dots were covalently linked to the DNA in order to generate the ECL signal. Using this steric hindrance hybridization method, the ECL signal of the biosensor were proportional to the concentration of IgG with a wide linear range and a 14 pM detection limit. Conceivably, the method can be expanded to the detection of a wide range of proteins for which homologous recognition elements are available.
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高影响因子
ACS Applied Bio Materials
·
2019
·
IF 0
Hongyan Cui,Jing Xia,Liuwei Zhang,Ming Qian,Hao Wang,Jingyun Wang,Qixian Chen
The surface properties of drug/gene delivery systems are critical important to their ultimate therapeutic performance. In the present studies, cytoplasmic membranes deriving from cancerous cells (Hep-G2) were attempted as the external integument onto the polycationic theranostic DNA delivery systems with the aim of diminishing unfavorable biointerfacial reactions of nanomedicine. Herein, a multiple of polycationic oligoethylenimine (OEI) segments were installed onto the surface of luminescent carbon quantum dots (CQD, facile bioimaging utilities) for complexation with plasmid DNA (pDNA) into DNA delivery constructs, followed by surface integument by cytoplasmic membranes. The subsequent investigations verified this strategic integument capable of shielding the unfavorable surface positive net charge of the polycationic DNA delivery constructs and thereby markedly diminishing the potential nonspecific reactions in biological milieu. Leadingly, improved biocompatibilities as well as additional protection of inner vulnerable DNA cargos from enzymatic degradation, have been accomplished. More importantly, preferential affinities to the homologous cells were identified as a result of this membrane integument based on facile fluorescence quantification for the intracellular CQD. Significant higher cellular uptake efficiency for the polycationic constructs based on Hep-G2 membrane integument was confirmed in the homologous Hep-G2 cells in contrast to the heterologous MCF-7 and HeLa cells (approximately 4-fold). Note that this homologous privilege was observed for the delivery constructs not only from cancerous HeLa and MCF-7 membrane integuments but also normal cells (COS-7), heralding the intriguing potentials of this membrane-integument strategy in pursuit of targeting functions. Eventually, gene expression activities were also determined to prevail in the homologous cells. Therefore, our proposed surface integument strategy by homologous cell membrane could imply an alternative facile and versatile avenue in construction of active-targeted nanomedicine.
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MICROCHIMICA ACTA
·
2018
·Vol. 185
·期 2
·1-9
·
IF 5.705
Chen Jun,Yu Chao,Gao Rufei,Geng Yanqing,Zhao Yilin,Niu Yazhen,Zhang Lei,Yu Yujie,He Junlin
A sandwich-type electrochemical DNA sensor is described for the detection of oligonucleotides typical for MECP2 gene mutations. Palladium nanoparticles (PdNPs) and platinum nanoparticles (PtNPs) were used to synthesize flower-like PdPt nanodendrites (NDs) by a one-pot method. The PdPt NDs possess a high specific surface area and excellent catalytic capabilities. They served as the carrier for the signal DNA probe (SP) and simultaneously catalyze the reduction of hydrogen peroxide (H 2 O 2 ). The PdPt NDs were modified with melamine, and this results in the formation of a PdPt-melamine network through stable interactions between the PdPt NDs and the three amino groups of each melamine molecule. The network exhibits excellent catalytic ability in enhancing the current signal response in the voltammetric detection of MECP2 gene mutation, best measured at −0.4 V vs. SCE and using H 2 O 2 as the electrochemical probe. In addition, gold nanoflowers were electrodeposited on the electrode interface in order to accelerate electron transfer and to capture the capture probe. The sensor is stable and can detect MECP2 gene mutations in the 1 fmol·L −1 to 1 nmol·L −1 concentration range, with a 0.33 fmol·L −1 lower detection limit at an S/N ratio of 3.
Schematic presentation of electrodes for the determination of the X-linked gene methyl-CpG-binding protein 2 (MECP2). The sensor is based on the electrooxidation of added H 2 O 2 by using the melamine modified palladium platinum bimetal nanodendrites as network signal amplification strategy. This versatile platform expands studies on the detection of monogenic disease.
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高影响因子
ACS Applied Bio Materials
·
2018
·
IF 0
Dawei Li,Dong Gao,Junjie Qi,Ran Chai,Yong Zhan,Chengfen Xing
DNA–protein interactions control DNA transcription, recombination, restriction, and replication, which play an important role in regulating life activities. We developed a new strategy to photothermally regulate DNA unzipping and binding to single-stranded binding protein (SSBP) based on the hybrid systems of graphene oxide (GO) and conjugated polymer. GO is applied as the photothermal modulator to activate the unzipping of dsDNA into ssDNA. Upon near-infrared (NIR) laser irradiation, the thermal melting transition of DNA is promoted, which results in much farther distance between poly[(9,9-bis(6′-N,N,N-trimethylammonium)hexyl)-fluorenylene phenylene dibromide] (PFP) and fluorescein labeled at the terminus of the DNA in comparison to that of dsDNA before NIR irradiation in the presence of GO. Therefore, the fluorescence resonance energy transfer (FRET) efficiency for PFP/fluorescein becomes weaker upon irradiation. Moreover, FRET efficiency could readily recover when the unzipped DNA hybridizes with SSBP. In this strategy, PFP/GO serves as detector and activator for the DNA unzipping and interacting with proteins, providing a facile and effective method for the regulation and detection of DNA–protein interactions.
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NUCLEIC ACIDS RESEARCH
·
2018
·Vol. 46
·期 7
·3284-3297
·
IF 11.561
Tong Qingyi,You Huijuan,Chen Xintao,Wang Kongchao,Sun Weiguang,Pei Yufeng,Zhao Xiaodan,Yuan Ming,Zhu Hucheng,Luo Zengwei,Zhang Yonghui
Despite All-trans retinoic acid (ATRA) has transformed acute promyelocytic leukemia (APL) from the most fatal to the most curable hematological cancer, there remains a clinical challenge that many high-risk APL patients who fail to achieve a complete molecular remission or relapse and become resistant to ATRA. Herein, we report that 5-(4-methoxyphenethyl)-[1, 3] dioxolo [4, 5-j] phenanthridin-6(5H)–one (ZYH005) exhibits specific anticancer effects on APL and ATRA-resistant APL in vitro and vivo, while shows negligible cytotoxic effect on non-cancerous cell lines and peripheral blood mononuclear cells from healthy donors. Using single-molecule magnetic tweezers and molecule docking, we demonstrate that ZYH005 is a DNA intercalator. Further mechanistic studies show that ZYH005 triggers DNA damage, and caspase-dependent degradation of the PML-RARa fusion protein. As a result, APL and ATRA-resistant APL cells underwent apoptosis upon ZYH005 treatment and this apoptosis-inducing effect is even stronger than that of arsenic trioxide and anticancer agents including 5-fluorouracil, cisplatin and doxorubicin. Moreover, ZYH005 represses leukemia development in vivo and prolongs the survival of both APL and ATRA-resistant APL mice. To our knowledge, ZYH005 is the first synthetic phenanthridinone derivative, which functions as a DNA intercalator and can serve as a potential candidate drug for APL, particularly for ATRA-resistant APL.
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高影响因子
MICROCHIMICA ACTA
·
2018
·Vol. 185
·期 10
·1-7
·
IF 5.705
Kong Caiyun,Gao Linna,Chen Zhengbo
An aptamer based assay is described for the colorimetric detection of adenosine. The presence of adenosine triggers the deformation of hairpin DNA oligonucleotide (HP1) containing adenosine aptamer and then hybridizes another unlabeled hairpin DNA oligonucleotide (HP2). This leads to the formation of a double strand with a blunt 3′ terminal. After exonuclease III (Exo III)-assisted degradation, the guanine-rich strand (GRS) is released from HP2. Hence, the adenosine-HP1 complex is released to the solution where it can hybridize another HP2 and initiate many cycles of the digestion reaction with the assistance of Exo III. This leads to the generation of a large number of GRS strands after multiple cycles. The GRS stabilize the red AuNPs against aggregation in the presence of potassium ions. If, however, GRS forms a G-quadruplex, it loses its ability to protect gold nanoparticles (AuNPs) from salt-induced AuNP aggregation. Therefore, the color of the solution changes from red to blue which can be visually observed. This colorimetric assay has a 0.13 nM detection limit and a wide linear range that extends from 5 nM to 1 μM.
Schematic presentation of a colorimetric aptamer biosensor for adenosine detection based on DNA cycling amplification and salt-induced aggregation of gold nanoparticles.
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高影响因子
Cellular and Molecular Bioengineering
·
2019
·Vol. 13
·期 1
·99-112
·
IF 2.477
Wang Yue,Li Xiaoli,Liu Lanlan,Liu Bingruo,Wang Feng,Chen Changsheng
Introduction Ultrasound-targeted microbubble destruction (UTMD) has been shown a promising approach for target-specific gene delivery and treatment of many diseases in the past decade. To improve the therapeutic potential of UTMD, the gene carrier of microbubbles should possess adequate DNA condensation capability and (or) specific cell or tissue selectivity. The tissue-targeted and ultrasound-targeted cationic microbubbles were developed to meet gene therapy. Methods A tissue-targeted stearic acid-inserted cationic microbubbles (SCMBs) were prepared for ultrasound-targeted gene delivery. Branched PEI was modified with stearic acid and further mixed with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and biot-1,2-distearoyl-sn-glycero-3-phosphoethanolamine- N -[methoxy (polyethylene glycol)-2000] (ammonium salt) (Biot-DSPE-PEG2000), intercellular adhesion molecule-1 (ICAM-1) antibody and plasmid DNA to prepare cationic microbubbles through ultrasonic hydration. The ICAM-1 antibody and plasmid DNA were expected to assemble to the surface of SCMBs via biotin-avidin interaction and electrostatic interaction, respectively. Results It was found that the SCMBs had higher zeta potential compared with neutral microbubbles (NMBs) and cationic microbubbles (CMBs). In contrast, DNA incorporated SCMBs4 showed negative potential, exhibiting good DNA-binding capacity. Confocal images showed that the HeLa cells were attached around by the SCMBs4 from the view of green fluorescence of fluorescein isothiocyanate-loaded IgG which conjugated to ICAM-1 antibody on their surface. After ultrasound treatment, HeLa cells treated with SCMBs exhibited slightly stronger red fluorescence under confocal laser scanning microscope, indicating a synergistic promotion for transfection efficiency. Conclusions This tissue- and ultrasound-targeted cationic microbubble demonstrated here showed a promising strategy for improving gene therapy in the future.
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高影响因子
Nanomaterials
·
2019
·Vol. 9
·期 8
·1154
·
IF 4.034
Wen Yang,Jing Yu,Xiangtai Xi,Yang Sun,Yiming Shen,Weiwei Yue,Chao Zhang,Shouzhen Jiang
In this paper, a graphene/ITO nanorod metamaterial/U-bent-annealing (Gr/ITO-NM/U-bent-A)-based U-bent optical fiber local surface plasmon resonance (LSPR) sensor is presented and demonstrated for DNA detection. The proposed sensor, compared with other conventional sensors, exhibits higher sensitivity, lower cost, as well as better biological affinity and oxidize resistance. Besides, it has a structure of an original Indium Tin Oxides (ITO) nanocolumn array coated with graphene, allowing the sensor to exert significant bulk plasmon resonance effect. Moreover, for its discontinuous structure, a larger specific surface area is created to accommodate more biomolecules, thus maximizing the biological properties. The fabricated sensors exhibit great performance (690.7 nm/RIU) in alcohol solution testing. Furthermore, it also exhibits an excellent linear response (R2= 0.998) to the target DNA with respective concentrations from 0.1 to 100 nM suggesting the promising medical applications of such sensors.Keywords:localized surface plasmon resonance biosensor;U-bent fiber;ITO metamaterials;high sensitivity;specificity deteection
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高影响因子
BIOSENSORS & BIOELECTRONICS
·
2024
·
IF 10.7
Tai Ye,Yimin Xu,Haohao Chen,Min Yuan,Hui Cao,Liling Hao,Xiuxiu Wu,Fengqin Yin,Fei Xu
Owing to advantage in high sensitivity and fast response, aptamer based electrochemical biosensors have attracted much more attention. However, inappropriate interfacial engineering strategy leads to poor recognition performance, which ascribe to the following factors of immobilized oligonucleotide strand including steric hindrance, interchain entanglement, and unfavorable conformation. In this work, we proposed a DNA tetrahedron based diblock aptamer immobilized strategy for the construction of label-free electrochemical biosensor. The diblock aptamer sequence is composite of T-rich anchor domain and recognition domain, where T-rich domain enabling anchored on the edge of DNA tetrahedron via Hoogsteen hydrogen bond at neutral condition. The DNA tetrahedron scaffold offers an appropriate lateral space for target recognition of diblock aptamer. More importantly, this trivalent aptamer recognition interface can be regenerated by simply adjusting the pH environment to alkaline, resulting in the dissociation of diblock aptamer. Under the optimum condition, proposed electrochemical aptasensor manifested a satisfied sensitivity for aminoglycosides antibiotic, kanamycin with a limit of detection of 0.69 nM, which is 45-fold lower than traditional Au–S immobilization strategy. Moreover, the proposed aptasensor had also successfully been extended to ampicillin detection by changing the sequence of recognition domain in diblock aptamer. This work paves a new way for the rational design of aptamer-based electrochemical sensor.
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高影响因子
ACS Omega
·
2024
·
IF 3.7
Ling Yang,Chunxiang Che,Mengfan Guo,Chunwei Fan,Lina Sun,Shanshan Chen
MicroRNAs (miRNAs), a class of small molecules with important regulatory functions, have been widely used in biosensing as biomarkers for the early diagnosis of various diseases (such as osteoporosis). Therefore, it is necessary to develop a miRNA detection platform with high sensitivity and specificity. Herein, an upconversion biosensor based on fluorescent resonant energy transfer (FRET) for the detection of miRNAs was developed. Gold nanoparticles (AuNPs, fluorescence acceptors) were conjugated with aptamers, while upconversion nanoparticles (UCNPs, fluorescence donors) were functionalized with the corresponding complementary DNA (cDNA). The upconversion luminescence (UCL) is quenched vis FRET due to the good overlap between UCNP fluorescence emission and AuNP absorption. In the presence of the target miRNA, the aptamers preferentially bind to the miRNA, thereby dissociating the UCNP-cDNA from the AuNP-aptamers, resulting in the recovery of the UCL. The UCL recovery efficiency increased in a miRNA concentration-dependent manner, which supported the principle of miRNA quantification. The UCNP-based FRET biosensor exhibited sensitive detection of miRNA-21 (as a model analyte) with low limit of detection of 5.91 pM. In addition, depending on the near-infrared excitation and a simple complementary binding reaction during the detection process, the designed biosensor not only effectively eliminated the autofluorescence but also reduced the detection time.
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高影响因子
MICROCHIMICA ACTA
·
2024
·Vol. 191
·期 2
·1-8
·
IF 5.3
Ou Dan,Yan Huixian,Chen Zuanguang
Based on the electrochemical impedance method, a marker-free biosensor with aptamer as a biometric element was developed for the determination of doxorubicin (DOX). By combining aptamer with rigid tetrahedral DNA nanostructures (TDNs) and fixing them on the surface of gold electrode (GE) as biometric elements, the density and directivity of surface nanoprobes improved, and DOX was captured with high sensitivity and specificity. DOX was captured by immobilized aptamers on the GE, which inhibited electron transfer between the GE and [Fe(CN)6] 3− / 4− in solution, resulting in a change in electrochemical impedance. When the DOX concentration was between 10.0 and 100.0 nM, the aptasensor showed a linear relationship with charge transfer resistance, the relative standard deviation (RSD) ranged from 3.6 to 5.9%, and the detection limit (LOD) was 3.0 nM. This technique offered a successful performance for the determination of the target analyte in serum samples with recovery in the range 97.0 to 99.6% and RSD ranged from 4.8 to 6.5%. This method displayed the advantages of fast response speed, good selectivity, and simple sensor structure and showed potential application in therapeutic drug monitoring. Graphical Abstract
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高影响因子
ACTA PHARMACOLOGICA SINICA
·
2024
·
IF 6.9
You Yi-ping,Yan Liang,Ke Hua-yu,Li Ya-ping,Shi Zi-jian,Zhou Zhi-ya,Yang Hai-yan,Yuan Tao,Gan Ying-qing,Lu Na,Xu Li-hui,Hu Bo,Ou-Yang Dong-yun,Zha Qing-bing,He Xian-hui
PANoptosis is an emerging form of regulated cell death (RCD) characterized by simultaneous activation of pyroptotic, apoptotic, and necroptotic signaling that not only participates in pathologies of inflammatory diseases but also has a critical role against pathogenic infections. Targeting PANoptosis represents a promising therapeutic strategy for related inflammatory diseases, but identification of inhibitors for PANoptosis remains an unmet demand. Baicalin (黄芩苷) is an active flavonoid isolated from Scutellaria baicalensis Georgi (Huangqin), a traditional Chinese medicinal herb used for heat-clearing and detoxifying. Numerous studies suggest that baicalin possesses inhibitory activities on various forms of RCD including apoptosis/secondary necrosis, pyroptosis, and necroptosis, thereby mitigating inflammatory responses. In this study we investigated the effects of baicalin on PANoptosis in macrophage cellular models. Primary macrophages (BMDMs) or J774A.1 macrophage cells were treated with 5Z-7-oxozeaenol (OXO, an inhibitor for TAK1) in combination with TNF-α or LPS. We showed that OXO plus TNF-α or LPS induced robust lytic cell death, which was dose-dependently inhibited by baicalin (50−200 μM). We demonstrated that PANoptosis induction was accompanied by overt mitochondrial injury, mitochondrial DNA (mtDNA) release and Z-DNA formation. Z-DNA was formed from cytosolic oxidized mtDNA. Both oxidized mtDNA and mitochondrial Z-DNA puncta were co-localized with the PANoptosome (including ZBP1, RIPK3, ASC, and caspase-8), a platform for mediating PANoptosis. Intriguingly, baicalin not only prevented mitochondrial injury but also blocked mtDNA release, Z-DNA formation and PANoptosome assembly. Knockdown of ZBP1 markedly decreased PANoptotic cell death. In a mouse model of hemophagocytic lymphohistiocytosis (HLH), administration of baicalin (200 mg/kg, i.g., for 4 times) significantly mitigated lung and liver injury and reduced levels of serum TNF-α and IFN-γ, concomitant with decreased levels of PANoptosis hallmarks in these organs. Baicalin also abrogated the hallmarks of PANoptosis in liver-resident macrophages (Kupffer cells) in HLH mice. Collectively, our results demonstrate that baicalin inhibits PANoptosis in macrophages by blocking mitochondrial Z-DNA formation and ZBP1-PANoptosome assembly, thus conferring protection against inflammatory diseases. PANoptosis is a form of regulated cell death displaying simultaneous activation of pyroptotic, apoptotic, and necroptotic signaling. This study shows that induction of PANoptosis is linked to mitochondrial dysfunction and mitochondrial Z-DNA formation. Baicalin inhibits PANoptosis in macrophages in vitro via blocking mitochondrial dysfunction and the mitochondrial Z-DNA formation and thereby impeding the assembly of ZBP1-associated PANoptosome. In a mouse model of hemophagocytic lymphohistiocytosis (HLH), baicalin inhibits the activation of PANoptotic signaling in liver-resident macrophages (Kupffer cells) in vivo, thus mitigating systemic inflammation and multiple organ injury in mice.
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高影响因子
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