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dna tetrahedron-based split aptamer probes for reliable imaging of ATP in living cells

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Chinese Chemical Letters 2023年第3期34卷 153-156页

作者： Lie Li Jie Wang Huishan Jiang Xiaohong Wen Mei Yang Suping Li Qiuping Guo Kemin Wang State Key Laboratory of Chemo/Biosensing and Chemometrics College of BiologyCollege of Chemistry and Chemical EngineeringHunan UniversityState Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan ProvinceChangsha 410082China

Accurate detection and imaging of adenosine triphosphate(ATP)expression levels in living cells is of great value for understanding cell metabolism,physiological activities,and pathologic ***,we developed a dna tetrahedron-based split aptamer probe(TD probe)for ratiometric fluorescence imaging of ATP in living *** TD probe is constructed by hybridizing two split ATP aptamer probes(Apt-a and Apt-b)to a dna tetrahedron assembled by four dna oligonucleotides(T1,T2,T3 and T4).In the presence of ATP,the TD probe will alter its structure from the open to closed state,thus bringing the separated donor and acceptor fluorophores into close proximity for high fluorescence resonance energy transfer(FRET)*** TD probe exhibits low cytotoxicity,efficient cell internalization and good biological ***,based on the FRET“off”to“on”signal output mode,the TD probe can effectively avoid false-positive signals from complex biological matrices,which is significant for long-term reliable imaging in living *** addition,by changing the split aptamers attached to dna tetrahedron,the proposed strategy may be extended for detecting various intracellular ***,this strategy provides a valuable sensing platform for biomarkers analysis in living cells,thus having great potential for early clinical diagnosis and therapeutic evaluation.

关键词： Adenosine triphosphate dna tetrahedron Split aptamer Fluorescence resonance energy transfer Living cell imaging

pH-controlled dnazymes： Rational design and their applications in dna-machinery devices

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Nano Research 2016年第10期9卷 3084-3092页

作者： Yuqi Chen Yanyan Song Zhiyong He Zijing Wang Wenting Liu FuanWang Xiaolian Zhang Xiang Zhou College of Chemistry and Molecular Sciences The Institute for Advanced Studies Wuhan University Wuhan 430072 China School of Medicine Wuhan University Wuhan 430071 China

The availability and reliability of strategies for molecular biosensing over a finely adjustable dynamic range is essential to enhance the understanding and control of vital biological process. To expand the versatility and utility of nucleic acid- related enzymes, we demonstrated a rational approach to acquiring tunable, pH-dependent deoxyribozymes （dnazymes） with catalytic activities and response sensitivities that can be tuned through a simple change in solution pH. To do this, we capitalized upon the pH dependence of Hoogsteen interactions and designed i-motif- and triplex-based dnazymes that can be finely regulated with high precision over a physiologically relevant pH interval. The modified dnazymes are dependent upon pH for efficient cleavage of substrates, and their catalytic performance can be tuned by regulating the sequence of inserted i-motif/triplex structures. The principle of tunable, pH-dependent dnazymes provides the opportunity to engineer pH-controlled dna-machinery devices with unprecedented sensitivity to pH changes. For example, we constructed a dna-walker device, the stepping rate of which could be adjusted by simply modulating solution pH within an interval of 5.6 to 7.4, as well as a dna tetrahedron that can be opened at pH 6.4 and kept closed at pH 7.4. The potential of this approach is not limited to serve as pH-dependent devices, but rather may be combined with other elements to expand their practical usefulness.

关键词： pH iMNAzyme TNAzyme dna walker dna tetrahedron

An ultrasensitive aptasensor for prostate specific antigen assay based on Exonuclease T-aided cyclic cleavage

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Science China Chemistry 2018年第4期61卷 393-396页

作者： Guangxing Liu Tian Zhang Yuguo Tang Peng Miao CAS Key Laboratory of Bio-Medical Diagnostics Suzhou Institute of Biomedical Engineering and TechnologyChinese Academy of SciencesSuzhou 215163China University of Science and Technology of China Hefei 230026China

An ultrasensitive electrochemical aptasensor is presented for prostate specific antigen(PSA) detection. dna tetrahedronaptamer is designed, which not only facilitates the molecular self-assembly events,but also improves the recognition efficiency between PSA and aptamer sequence on the electrode interface. The dna conformation on top of dna tetrahedron changes accordingly, which can be further digested by Exonuclease T(Exo T), a type of single-strand specific nuclease. Electrochemical species are removed synchronously and the initial PSA level can thus be determined. A linear range from 0.5 pg mL^(-1) to50 ng mL^(-1) is achieved with the limit of detection(LOD) as low as 0.15 pg mL^(-1). Moreover, this proposed method is highly selective and is successfully applied to determine PSA in human serum samples.

关键词： prostate specific antigen aptamer dna tetrahedron Exonuclease T square wave voltammetry.

Synchronous conjugation of i-motif dna and therapeutic siRNA on the vertexes of tetrahedral dna nanocages for efficient gene silence

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Acta Pharmaceutica Sinica B 2021年第10期11卷 3286-3296页

作者： Xiu Han Xiang Xu Ziheng Wu Zhenghong Wu Xiaole Qi Key Laboratory of Modern Chinese Medicines China Pharmaceutical UniversityNanjing 210009China Medical School of Nanjing University Nanjing UniversityNanjing 210093China Parkville Campus Monash UniversityVIC 3052Australia

The functionality of dna biomacromolecules has been widely excavated,as therapeutic drugs,carriers,and functionalized modification *** this study,we developed a series of dna tetrahedron nanocages(Td),via synchronous conjugating different numbers of i-(X)and therapeutic siRNA on four vertexes of tetrahedral dna nanocage(aX-Td@bsiRNA,a+b=4).This i-motif-conjugated Td exhibited good endosomal escape behaviours in A549 tumor cells,and the escape efficiency was affected by the number of ***,the downregulating mRNA and protein expression level of epidermal growth factor receptor(EGFR)caused by this siRNA embedded Td were verified in A549 *** tumor growth inhibition efficiency of the 2X-Td@2siRNA treated group in tumorbearing mice was significantly higher than that of non-i-motif-conjugated Td@2siRNA(3.14-fold)and free siRNA(3.63-fold).These results demonstrate a general strategy for endowing dna nanostructures with endosomal escape behaviours to achieve effective in vivo gene delivery and therapy.

关键词： i-motif siRNA Gene delivery dna tetrahedron Endosomal escape Cancer Gene silence Biocompatibility

Nucleic acid nanoassembly-enhanced RNA therapeutics and diagnosis

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Acta Pharmaceutica Sinica B 2023年第3期13卷 916-941页

作者： Mengnan Zhao Rujing Wang Kunmeng Yang Yuhong Jiang Yachen Peng Yuke Li Zhen Zhang Jianxun Ding Sanjun Shi State Key Laboratory of Southwestern Chinese Medicine Resources School of PharmacyChengdu University of Traditional Chinese MedicineChengdu 611137China The First Norman Bethune College of Clinical Medicine Jilin UniversityChangchun 130061China School of Life Science and Engineering Southwest Jiaotong UniversityChengdu 610031China Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China Department of Orthopedics China-Japan Union Hospital of Jilin UniversityChangchun 130033China

RNAs are involved in the crucial processes of disease progression and have emerged as powerful therapeutic targets and diagnostic ***,efficient delivery of therapeutic RNA to the targeted location and precise detection of RNA markers remains ***,more and more attention has been paid to applying nucleic acid nanoassemblies in diagnosing and *** to the flexibility and deformability of nucleic acids,the nanoassemblies could be fabricated with different shapes and *** hybridization,nucleic acid nanoassemblies,including dna and RNA nanostructures,can be applied to enhance RNA therapeutics and *** review briefly introduces the construction and properties of different nucleic acid nanoassemblies and their applications for RNA therapy and diagnosis and makes further prospects for their development.

关键词： Nucleic acid nanoassembly dna nanotechnology RNA nanotechnology RNA therapy RNA detection dna origami RNA interference dna tetrahedron

Tetrahedral dna Nanostructure-modified Gold Nanorod-based Anticancer Nanomaterials for Combined Photothermal Therapy and Chemotherapy

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Biomedical and Environmental Sciences 2022年第12期35卷 1115-1125页

作者： WU Hao XU Jiang Shan LI Yan Hong WU Xing Han HU Wei LIU Meng Die SUN Qiang GUO Bin Medical School of Chinese PLA Beijing 100853China Department of Stomatology the First Medical CentreChinese PLA General HospitalBeijing 100853China College of Biomedical Engineering Sichuan UniversityChengdu 610064SichuanChina Institute of Medical Laboratory Animal Science CAMS&PUMCBeijing 100021China State Key Laboratory of Oral Disease National Clinical Research Center for Oral DiseasesWest China College of StomatologySichuan UniversityChengdu 610064SichuanChina

Objective To develop an effective treatment strategy to simultaneously avoid fatal adverse effects in the treatment of oral cancer,combination therapy has been explored because of its multiple *** work aims to develop a novel type of gold-nanorod-based nanomaterials decorated with tetrahedral dna nanostructures(TDN)carrying antitumor drugs,namely,GNR@TDN-DOX *** In the designed structure,TDN,with a three-dimensional geometry composed of dna strands,can provide GC base pairs for binding with the anticancer drug doxorubicin(DOX).The photothermal heating properties,biocompatibility properties,and antitumor performance of obtained GNR@TDN-DOX nanocomposites were investigated to assess their application potential in tumor *** Systematic studies have shown that the obtained GNR@TDN-DOX nanocomposites have high photothermal conversion under the illumination of an 808-nm infrared laser,leading to effective antitumor *** addition,the cell viability study shows that GNR@TDN-DOX nanocomposites have good *** vitro studies based on A375 cells show that the GNR@TDN-DOX nanocomposites can effectively eliminate cancer cells because of the combination of photothermal therapy induced by GNRS and chemotherapy induced by TDN-carrying *** result shows that the obtained GNR@TDN-DOX nanocomposites have efficient cellular uptake and lysosome escape ability,together with their nuclear uptake behavior,which results in a significant antitumor *** This work has demonstrated a potential nanoplatform for anticancer applications.

关键词： Nanomaterials dna tetrahedron Gold nanorod Combination therapy

Gold nanorods/tetrahedral dna composites for chemo-photothermal therapy

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Regenerative Biomaterials 2022年第1期9卷 404-413页

作者： Ziyun He Qiusheng Wang Nan Zhang Jianqin Yan Li Li Jun Cao Bin He National Engineering Research Center for Biomaterials College of Biomedical EngineeringSichuan UniversityChengdu 610064China Department of Pharmaceutics School of PharmacyQingdao UniversityQingdao 266073China

Combination therapy is extensively developed for cancer treatment in recent years due to its high ***,we constructed a nanocomposite based on gold nanorods(GNRs)and drug-loaded tetrahedral dna nanostructures(TDN)for chemophotothermal combinational ***-tumor drug doxorubicin(DOX)was loaded via the insertion within GC base pairs of *** aptamer AS1411 was attached to the apex of TDN(ATDN)to target tumor *** DOX-loaded dna tetrahedron(ATDN-DOX)was compressed by the GNRs coated with PEI(GNRs@ATDN-DOX)to realize the photothermal function and lysosome *** under the illumination of 808nm infrared laser showed high photothermal conversion and stability due to the protection of PEI *** drug-loading capacity of ATDN-DOX was as high as 314 DOX molecules in per *** positive charge of PEI in GNRs@ATDN-DOX nanocomposites was utilized to achieve excellent cell penetration and induce proton sponge effect for lysosomal *** nanocomposites presented HeLa and 4T1 cells targeting and resulted in efficient anticancer activity.

关键词： nanocomposite dna tetrahedron gold nanorod chemo-photothermal therapy

基于四面体dna和杂交链式反应构建的用于检测癌胚抗原的免标记型电化学传感策略（英文）

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基于四面体DNA和杂交链式反应构建的用于检测癌胚抗原的免标记型...