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  • Enhanced Targeted Gene Transduction: AAV2 Vectors Conjugated to Multiple Aptamers via Reducible Disulfide Linkages

    • 摘要:

      Enhanced targeted gene transduction by AAV2 vectors is achieved by linking the vector to multiple sgc8 aptamers, which are selective for cell membrane protein PTK7. Aptamer molecules are conjugated to multiple sites on a DNA dendrimer (G-sgc8), which is then linked to AAV2 via a dithiobis(succinimidyl propionate) cross-linker containing a disulfide group, which can facilitate the release of AAV2 vectors by reaction with the reduced form of intracellular glutathione. The G-sgc8-AAV2 vectors showed a 21-fold enhancement in binding affinity and an enhanced ability to protect sgc8 aptamers against nuclease degradation to cells expressing PTK7 compared to single aptamer-AAV2 conjugates. The transduction efficiency was tested by loading AAV2 with the gene for green fluorescent protein. Therefore, this modified recombinant vector is an attractive and promising tool for targeted biomedical applications.

    • 作者:

      Wu Yuan    Liqin Zhang    Cui Cheng    Cansiz Sena    Liang Hao    Cuichen Wu.    Ting Teng    Chen Weijun    Liu Yuan    Hou Weijia    Zhang Xiao Bing    谭蔚泓    

    • 刊名:

      Journal of the American Chemical Society

    • 在线出版时间:

      2018

  • Construction of self-powered cytosensing device based on ZnO nanodisks@g-C3N4 quantum dots and application in the detection of CCRF-CEM cells

    • 摘要:

      We herein report a self-powered and renewable cytosensing device based on ZnO nanodisks(NDs)@g-CN quantum dots. The device features enhanced photoelectrochemical (PEC) activity compared to ZnO NDs or g-CN QDs alone. The enhanced PEC ability is attributed to the synergistic effect of the high visible light sensitivity of g-CN QDs and the staggered band alignment heterojunction structure with suitable band offset, which affords higher photoelectron transfer and separation efficiency. In addition, the hybridization of g-CN QDs further accelerates interfacial electron transfer and blocks recombination between electron donors and photogenerated holes. The device was applied to the detection of CCRF-CEM cells. By conjugation to Sgc8c aptamer, which preferentially interacts with membrane-bound PTK7 on CCRF-CEM membranes, capture of target CCRF-CEM cells resulted in a decrease in apparent power output, which was then exploited for the ultrasensitive detection of the target cells. This decrease in power output can be recovered by simply increasing the temperature to release the cells, thus recycling the cytosensing performance. The device displayed a linear relationship between the change of power output and the logarithm of the cell concentration from 20 to 20,000 cell/mL (R = 0.9837) and a detection limit down to 20 cell/mL, as well as excellent selectivity and reproducibility. Thus, this ZnO NDs@g-CN QDs-based device exhibits high potential for the detection of CCRF-CEM cells.

    • 作者:

      Xuehui Pang    Cui Cheng    Su Minhui    王姚光    Qin Wei    谭蔚泓    

    • 刊名:

      Nano Energy

    • 在线出版时间:

      2018

  • Bioapplications of cell-SELEX-generated aptamers in cancer diagnostics, therapeutics, theranostics and biomarker discovery: A comprehensive review

    • 摘要:

      Currently, functional single-stranded oligonucleotide probes, termed aptamers, generated by an iterative technology, Systematic Evolution of Ligands by Exponential Enrichment (SELEX), are utilized to selectively target molecules or cells with high affinity. Aptamers hold considerable promise as multifunctional molecules or conjugates for challenging nanotechnologies or bioapplications now and in the future. In this review, we first describe recent endeavors to select aptamers towards live cancer cells via cell-SELEX. We then introduce several characteristic applications of selected aptamers, especially in imaging, drug delivery and therapy. In part, these advances have been made possible via synthesis of aptamer-based nanomaterials, which, by their sizes, shapes, and physicochemical properties, allow such aptamer-nanomaterial complexes to function as signal reporters or drug carriers. We also describe how these aptamer-based molecular tools contribute to cancer biomarker discovery through high-affinity recognition of membrane protein receptors.

    • 作者:

      Xuehui Pang    Cui Cheng    Wan Shuo    Jiang Ying    Zhang Liang-Liang    Lian Xia    Li Long    Li Xiaowei    谭蔚泓    

    • 刊名:

      Cancers

    • 在线出版时间:

      2018

  • An MTH1-targeted nanosystem for enhanced PDT: Via improving cellular sensitivity to reactive oxygen species

    • 摘要:

      Herein, we developed a strategy to attack the cancer cell defense system against reactive oxygen species to improve photodynamic therapy efficacy with a Ce6@MSN@MTH1 siRNA nanosystem, which was demonstrated to improve cellular sensitivity to reactive oxygen species through suppressing MTH1 protein in cancer cells.

    • 作者:

      Fan Huanhuan    Zhang Lili    Xiaoxiao Hu    Zilong Zhao    Bai Huarong    Fu Xiaoyi    Yan Guobei    Liang Li Hui    Zhang Xiao Bing    谭蔚泓    

    • 刊名:

      Chemical Communications

    • 在线出版时间:

      2018

  • Fluorinated DNA Micelles: Synthesis and Properties

    • 摘要:

      Creating new functional building blocks that expand the versatility of nanostructures depends on bottom-up self-assembly of amphiphilic biomolecules. Inspired by the unique physicochemical properties of hydrophobic perfluorocarbons, coupled with the powerful functions of nucleic acids, we herein report the synthesis of a series of diperfluorodecyl-DNA conjugates (PF-DNA) which can efficiently self-assemble into micelles in aqueous solution. Based on the micelle structure, both target binding affinity and enzymatic resistance of the DNA probe can be enhanced. In addition, based on the hydrophobic effect, the PF-DNA micelles (PFDM) can actively anchor onto the cell membrane, offering a promising tool for cell-surface engineering. Finally, the PFDM can enter cells, which is significant for designing carriers for intracellular delivery. The combined advantages of the DNA micelle structure and the unique physicochemical properties of perfluorocarbons make these PFDM promising for applications in bioimaging and biomedicine.

    • 作者:

      Zou Jianmei    Jin Cheng    Ruowen Wang    Kuai Hailan    Zhang Lili    Xiaobing Zhang    Li Juan    Qui Liping    谭蔚泓    

    • 刊名:

      Analytical Chemistry

    • 在线出版时间:

      2018

  • DNA-Based Dynamic Reaction Networks

    • 摘要:

      Deriving from logical and mechanical interactions between DNA strands and complexes, DNA-based artificial reaction networks (RNs) are attractive for their high programmability, as well as cascading and fan-out ability, which are similar to the basic principles of electronic logic gates. Arising from the dream of creating novel computing mechanisms, researchers have placed high hopes on the development of DNA-based dynamic RNs and have strived to establish the basic theories and operative strategies of these networks. This review starts by looking back on the evolution of DNA dynamic RNs; in particular’ the most significant applications in biochemistry occurring in recent years. Finally, we discuss the perspectives of DNA dynamic RNs and give a possible direction for the development of DNA circuits.

    • 作者:

      Ting Fu    Lyu Yifan    Liu Hui    Peng Ruizi    Xiaobing Zhang    Mao Ye    谭蔚泓    

    • 刊名:

      Trends in Biochemical Sciences

    • 在线出版时间:

      2018

  • Versatile: In situ synthesis of MnO2 nanolayers on upconversion nanoparticles and their application in activatable fluorescence and MRI imaging

    • 摘要:

      We have developed a simple and versatile strategy for in situ growth of MnO on the surfaces of oleic acid-capped hydrophobic upconversion nanoparticles (UCNPs) by optimizing the component concentrations in the Lemieux-von Rudloff reagent. The oxidation time was shortened by a factor of two compared to that of the reported method. This oxidation process has no obvious adverse effects on the phases of UCNPs. STEM, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FTIR) and energy-dispersive X-ray analysis (EDX) characterization demonstrated the successful growth of MnO on the surfaces of UCNPs. Furthermore, when the weight ratio of MnO/UCNPs reached (147.61 ± 17.63) μg mg, 50% of the initial upconversion luminescence of UCNPs was quenched, as revealed by fluorescence and inductively coupled plasma optical emission spectrometry (ICP-OES) results. The presence of the surface MnO precipitate not only confers high dispersity of UCNPs in water, but also allows further activatable magnetic resonance imaging (MRI) and fluorescence multimodal imaging after reduction to Mn by intracellular glutathione (GSH). A novel targeted drug carrier nanosystem was prepared to protect MnO from early decomposition in blood circulation by coating with mesoporous silica and capping with a gelatin nanolayer. Aptamer sgc8 was then attached to the surface of the gelatin nanolayer by covalent crosslinking to achieve targeted drug delivery. The results suggest that this nanosystem shows promise for further applications in cancer cell imaging and therapy.

    • 作者:

      Wu Yuan    Li Dan    Zhou Fang    Liang Hao    Liu Yuan    Hou Weijia    Quan Yuan    Xiaobing Zhang    谭蔚泓    

    • 刊名:

      Chemical Science

    • 在线出版时间:

      2018

  • Molecular Recognition and In-Vitro-Targeted Inhibition of Renal Cell Carcinoma Using a DNA Aptamer

    • 摘要:

      Renal cell carcinoma (RCC) is the most common malignant tumor of the urinary system, and it has a high frequency of local invasion and distant metastasis. Although multiple advances have been made in the diagnosis and therapy of RCC, the vast majority of patients with metastatic RCC remain incurable. In this study, an aptamer named SW-4 against RCC 786-O cells was identified from a known sequence pool. The identified aptamer exhibited high binding affinity for target cells with dissociation constants in the nanomolar range. Binding analysis revealed that SW-4 only bound to RCC 786-O cells, but not HEK293T cells or human proximal tubular HK-2 cells, indicating that SW-4 has excellent binding selectivity. By sequence optimization, the 26-nt truncated SW-4b demonstrated improved binding affinity, and it was internalized into target cells via caveolae-mediated endocytosis in a temperature-dependent manner. Furthermore, fluorescence imaging confirmed that SW-4b accumulated at tumor sites in 786-O xenograft nude mice models and specifically recognized clinical RCC tissues. Meanwhile, SW-4b inhibited proliferation of 786-O cells by arresting cell cycle progression at the S phase. Taken together, these results indicate that SW-4b is a potential candidate for development into a novel tool for diagnosis and targeted therapy of RCC.

    • 作者:

      Zhang Hui    Wang Zhibo    Xie Lin    Zhang Yibin    Deng Tanggang    Jianglin Li    Liu Jing    Xiong Wei    Zhang Lei    Zhang Lin    Peng Bo    He Leye    Mao Ye    Xiaoxiao Hu    谭蔚泓    

    • 刊名:

      Molecular Therapy - Nucleic Acids

    • 在线出版时间:

      2018

  • Aptamer-functionalized nano/micro-materials for clinical diagnosis: Isolation, release and bioanalysis of circulating tumor cells

    • 摘要:

      Detection of rare circulating tumor cells (CTCs) in peripheral blood is a challenging, but necessary, task in order to diagnose early onset of metastatic cancer and to monitor treatment efficacy. Over the last decade, step-up produced aptamers have attracted great attention in clinical diagnosis. They have offered great promise for a broader range of cell-specific recognition and isolation. In particular, aptamer-functionalized magnetic particles for selective extraction of target CTCs have shown reduced damage to cells and relatively simple operation. Also, efforts to develop aptamer-functionalized microchannel/microstructures able to efficiently isolate target CTCs are continuing, and these efforts have brought more advanced geometrically designed substrates. Various aptamer-mediated cell release techniques are being developed to enable subsequent biological studies. This article reviews some of these advances in aptamer-functionalized nano/micro-materials for CTCs isolation and methods for releasing captured CTCs from aptamer-functionalized surfaces. Biological studies of CTCs after release are also discussed.

    • 作者:

      Zhao Yaju    许丹科    谭蔚泓    

    • 刊名:

      Integrative Biology (United Kingdom)

    • 在线出版时间:

      2017

  • Multifunctional Molecular Beacon Micelles for Intracellular mRNA Imaging and Synergistic Therapy in Multidrug-Resistant Cancer Cells

    • 摘要:

      Multidrug resistance (MDR) resulting from overexpression of P-glycoprotein (Pgp) transporters increases the drug efflux and thereby limits the chemotherapeutic efficacy. It is desirable to administer both an MDR1 gene silencer and a chemotherapeutic agent in a sequential way to generate a synergistic therapeutic effect in multidrug-resistant cancer cells. Herein, an anti-MDR1 molecular beacon (MB)-based micelle (a-MBM) nanosystem is rationally designed. It is composed of a diacyllipid core densely packed with an MB corona. One of Pgp-transportable agents, doxorubicin (DOX), is encapsulated in the hydrophobic core of the micelle and in the stem sequence of MB. The a-MBM-DOX nanosystem shows an efficient self-delivery, enhanced enzymatic stability, excellent target selectivity, and high drug-loading capacity. With its relatively high enzymatic stability, a-MBM-DOX initially facilitates intracellular MDR1 mRNA imaging to distinguish multidrug-resistant and non-multidrug-resistant cells and subsequently downregulates the MDR1 gene expression owing to an antisense effect. After that, the MB corona is degraded, destroying the micellar nanostructure and releasing DOX, which result in a high accumulation of DOX in OVCAR8/ADR cells and a high chemotherapeutic efficacy because of successful restoration of drug sensitivity. This micelle approach has the potential for both visualizing MDR1 mRNA and overcoming MDR in a sequential and synergistic way.

    • 作者:

      Zhang Ruili    Gao Shi    Wang Zhongliang    韩达    Liu Lin    Qingjie Ma    谭蔚泓     Tian Jie    Xiaoyuan Chen   

    • 刊名:

      Advanced Functional Materials

    • 在线出版时间:

      2017

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