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Jian Wang, Mingxu You,
Guizhi Zhu,
Mohammed Ibrahim Shukoor,
Zhuo Chen,
Zilong Zhao,
Meghan B Altman,
Quan Yuan,
Zhi Zhu,
Yan Chen,
Cheng Zhi Huang,
Weihong Tan
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ABSTRACT: In this work, a DNA inter-strand replacement strategy for therapeutic activity is successfully designed for multimodal therapy. In this multimodal therapy, chlorin e6 (Ce6) photosensitizer molecules are used for photodynamic therapy (PDT), while aptamer-AuNRs, are used for selective binding to target cancer cells and for photothermal therapy (PTT) with near infrared laser irradiation. Aptamer Sgc8, which specifically targets leukemia T cells, is conjugated to an AuNR by a thiol-Au covalent bond and then hybridized with a Ce6-labeled photosensitizer/reporter to form a DNA double helix. When target cancer cells are absent, Ce6 is quenched and shows no PDT effect. However, when target cancer cells are present, the aptamer changes structure to release Ce6 to produce singlet oxygen for PDT upon light irradiation. Importantly, by combining photosensitizer and photothermal agents, PTT/PDT dual therapy supplies a more effective therapeutic outcome than either therapeutic modality alone.
Small 05/2013; · 8.35 Impact Factor
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ABSTRACT: Strand displacement cascades are commonly used to make dynamically assembled structures. Particularly, the concept of "toehold-mediated DNA branch migration reactions" has attracted considerable attention in relation to dynamic DNA nanostructures. However, it is a challenge to obtain and control the formation of pure 1:1 ratio DNA duplexes with toehold structures. Here, for the first time, we report a photocontrolled toehold formation method, which is based on the photocleavage of 2-nitrobenzyl linker-embedded DNA hairpin precursor structures. UV light irradiation (λ365 nm) of solutions containing these DNA hairpin structures causes the complete cleavage of the nitrobenzyl linker, and pure 1:1 DNA duplexes with toehold structures are easily formed. Our experimental results indicate that the amount of toehold can be controlled by simply changing the dose of UV irradiation and that the resulting toehold structures can be used for subsequent toehold-mediated DNA branch migration reactions, e.g., DNA hybridization chain reactions. This newly established method will find broad application in the construction of light-powered, controllable and dynamic DNA nanostructures or large-scale DNA circuits.
Journal of the American Chemical Society 05/2013; · 9.91 Impact Factor
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ABSTRACT: Lighting the way with DNA: Molecular beacon micelle flares (MBMFs), based on self-assembly of diacyllipid-molecular-beacon conjugates (L-MBs; see figure), have been developed for combined mRNA detection and gene therapy. These MBMFs were shown to inhibit a model gene in vitro and decrease the viability of cancer cells in culture.
Angewandte Chemie International Edition 01/2013; · 13.45 Impact Factor
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ABSTRACT: Western blot, enzyme linked immunosorbent assay (ELISA), and fluorescent fusion proteins are currently the most common methods for detecting recombinant proteins. However, the former two are cumbersome and time-consuming, and the latter method may interfere with the trafficking and function of the fused recombinant proteins. We report here a rapid, inexpensive, and simple approach to detect and quantify recombinant proteins using an anti-His-tag molecular beacon aptamer (HMBA). We demonstrated the technique by detection and quantitation of expressed recombinant proteins directly from E. coli cell lysate. The amount of expressed P78-His was determined to be 1.49 μg from the 20 μg cell lysate proteins. To the best of our knowledge, this is the first example directly measuring the concentration and expression yield of recombinant proteins from cell lysate, and the entire procedure required only 5 min.
Analytical Chemistry 08/2012; 84(19):8272-6. · 5.86 Impact Factor
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ABSTRACT: Recently, the specific hybridization of DNA molecules has been used to construct self-assembled devices, such as the mechanical device to mimic cellular protein motors in nature. Here, we present a new light-powered DNA mechanical device based on the photoisomerization of azobenzene moieties and toehold-mediated strand displacement. This autonomous and controllable device is capable of moving toward either end of the track, simply by switching the wavelength of light irradiation, either UV (365 nm) or visible (>450 nm). This light-controlled strategy can easily solve one main technical challenge for stepwise walking devices: the selection of routes in multipath systems. The principle employed in this study, photoisomerization-induced toehold length switching, could be further useful in the design of other mechanical devices, with the ultimate goal of rivaling molecular motors for cargo transport and macroscopic movement.
ACS Nano 07/2012; 6(9):7935-41. · 10.77 Impact Factor
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ABSTRACT: High quality nanocrystals have demonstrated substantial potential for biomedical applications. However, being generally hydrophobic, their use has been greatly limited by complicated and inefficient surface engineering that often fails to yield biocompatible nanocrystals with minimal aggregation in biological fluids and active targeting toward specific biomolecules. Using chimeric DNA molecules, we developed a one-step facile surface engineering method for hydrophobic nanocrystals. The procedure is simple and versatile, generating individual nanocrystals with multiple ligands. In addition, the resulting nanocrystals can actively and specifically target various molecular addresses, varying from nucleic acids to cancer cells. Together, the strategy developed here holds great promise in generating critical technologies needed for biomedical applications of nanocrystals.
Journal of the American Chemical Society 07/2012; 134(32):13164-7. · 9.91 Impact Factor
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ABSTRACT: Molecular recognition is fundamental to the specific interactions between molecules, of which the best known examples are antibody-antigen binding and cDNA hybridization. Reversible manipulation of the molecular recognition events is still a very challenging topic, and such studies are often performed at the molecular level. An important consideration is the collection of changes at the molecular level to provide macroscopic observables. This research makes use of photoresponsive molecular recognition for the fabrication of novel photoregulated dynamic materials. Specifically, a dynamic hydrogel was prepared by grafting azobenzene-tethered ssDNA and its cDNA to the hydrogel network. The macroscopic volume of the hydrogel can be manipulated through the photoreversible DNA hybridization controlled by alternate irradiation of UV and visible light. The effects of synthetic parameters including the concentration of DNA, polymer monomer, and permanent cross-linker are also discussed.
Journal of the American Chemical Society 06/2012; 134(29):12302-7. · 9.91 Impact Factor
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Jian Wang,
Guizhi Zhu, Mingxu You,
Erqun Song,
Mohammed Ibrahim Shukoor,
Kejing Zhang,
Meghan B Altman,
Yan Chen,
Zhi Zhu,
Cheng Zhi Huang,
Weihong Tan
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ABSTRACT: An aptamer switch probe (ASP) linking chlorin e6 (Ce6), a photosensitizer molecule, to the surface of gold nanorods (AuNRs) was used to target cancer cells for photodynamic therapy (PDT) and photothermal therapy (PTT). In the presence of target cancer cells, the ASP changes conformation to drive Ce6 away from the gold surface, thereby producing singlet oxygen for PDT upon light irradiation. Since each AuNR is modified with many ASP-Ce6 molecules, the AuNR-ASP-Ce6 conjugate yields enhanced binding and therapeutic effect by the added ability to carry many photosensitizers. In addition, absorption of radiation by the gold nanorods enables further cell destruction by the photothermal effect. Consequently, this multimodal AuNR-ASP-Ce6 conjugate offers a remarkably improved and synergistic therapeutic effect compared to PTT or PDT alone, providing high specificity and therapeutic efficiency, which can be generalized to other types of cancer therapies.
ACS Nano 05/2012; 6(6):5070-7. · 10.77 Impact Factor
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ABSTRACT: A single anthryl appended meso-tetraphenylporphyrin (TPP) dyad has been synthesized and applied in fluorescence sensing of
iodine based on the intramolecular excitation energy transfer. The molecular recognition of the sensor is based on the interaction
of iodine with inner anthracene moiety of the dyad, while the signal reporter for the recognition process is the TPP fluorescence
quenching. Because the emission spectrum of anthracene is largely overlapped with the Soret band absorption of TPP, intramolecular
excitation energy transfer interaction occurs between the donor, anthracene and acceptor, TPP. This energy transfer leads
to TPP fluorescence emission by excitation of anthracene. The sensor was constructed by immobilizing the dyad in a plasticized
poly(vinyl chloride) (PVC) membrane. The sensing membrane shows higher sensitivity compared to the sensors by using anthracene,
TPP, or a mixture of anthracene and TPP as sensing materials. Under the optimum conditions, iodine in a sample solution can
be determined from 2.04 to 23.6 mmol·L−1 with a detection limit of 33 nmol·L−1. The sensing membrane shows satisfactory response characteristics including good reproducibility, reversibility and stability,
as well as the short response time of less than 60 s. Except for Cr2O72− and MnO4−, other common metal ions and anions in foodstuff do not interfere with iodine determination. The proposed method was applied
in the determination of iodine in table salt samples. The results agree well with those obtained by other methods.
Science in China Series B Chemistry 04/2012; 52(6):793-801. · 1.20 Impact Factor
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ABSTRACT: A nanorobot is able to perform autonomous locomotion and control the initiation, termination, and velocity by light. In their Communication on page 2457 ff., X. Zhang, W. Tan, and co-workers report the design of a DNA walking device by incorporating photosensitive moieties within DNA enzyme analogue structures. Based on the phenomenon of pyrene-assisted photolysis of disulfide bonds, this nanorobot shows the operational freedom and mechanical speed reminiscent of protein motors.
Angewandte Chemie International Edition 03/2012; 51(10):2511. · 13.45 Impact Factor
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ABSTRACT: Regulatable nanorobots: A DNA-based walking device was designed that is capable of autonomous locomotion, with light control of initiation, termination, and velocity. This device is reminiscent of cellular protein motors in nature, especially those of green plants.
Angewandte Chemie International Edition 03/2012; 51(10):2457-60. · 13.45 Impact Factor
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Chemistry 01/2012; 18(5):1286-9. · 5.93 Impact Factor
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ABSTRACT: Molecular beacons (MBs) represent a class of nucleic acid probes with unique DNA hairpin structures that specifically target complementary DNA or RNA. The inherent "OFF" to "ON" signal transduction mechanism of MBs makes them promising molecular probes for real-time imaging of DNA/RNA in living cells. However, conventional MBs have been challenged with such issues as false-positive signals and poor biostability in complex cellular matrices. This paper describes the novel engineering steps used to improve the fluorescence signal and reduce to background fluorescence, as well as the incorporation of unnatural nucleotide bases to increase the resistance of MBs to nuclease degradation for application in such fields as chemical analysis, biotechnology, and clinical medicine. The applications of these de novo MBs for single-cell imaging will be also discussed.
International journal of molecular imaging. 01/2012; 2012:501579.
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ABSTRACT: Future smart nanostructures will have to rely on molecular assembly for unique or advanced desired functions. For example, the evolved ribosome in nature is one example of functional self-assembly of nucleic acids and proteins employed in nature to perform specific tasks. Artificial self-assembled nanodevices have also been developed to mimic key biofunctions, and various nucleic acid- and protein-based functional nanoassemblies have been reported. However, functionally regulating these nanostructures is still a major challenge. Here we report a general approach to fine-tune the catalytic function of DNA-enzymatic nanosized assemblies by taking advantage of the trans-cis isomerization of azobenzene molecules. To the best of our knowledge, this is the first study to precisely modulate the structures and functions of an enzymatic assembly based on light-induced DNA scaffold switching. Via photocontrolled DNA conformational switching, the proximity of multiple enzyme catalytic centers can be adjusted, as well as the catalytic efficiency of cofactor-mediated DNAzymes. We expect that this approach will lead to the advancement of DNA-enzymatic functional nanostructures in future biomedical and analytical applications.
ACS Nano 11/2011; 5(12):10090-5. · 10.77 Impact Factor
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ABSTRACT: Because of their easily modified chemical structures and wide range of targets, aptamers are ideal candidates for various applications, such as biomarker discovery, target diagnosis, molecular imaging, and drug delivery. Aptamers are oligonucleotide sequences that can bind to their targets specifically via unique three dimensional (3-D) structures. Usually, aptamers are obtained from repeated rounds of in vitro or in vivo selection termed SELEX (Systematic Evolution of Ligands by EXponential enrichment), which can generate aptamers with high affinity and specificity for many kinds of targets, such as biomedically important proteins and even cancer cells. In this review, some basic principles and recent developments in the design of SELEX process are discussed, hopefully to provide some guidelines towards performing more efficient aptamer isolation procedures. Moreover, the biomedical and bioanalytical applications of aptamers are further reviewed, based on some smart biochemical modifications of these oligonucleotide structures.
Current Medicinal Chemistry 08/2011; 18(27):4117-25. · 4.86 Impact Factor
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Angewandte Chemie International Edition 06/2011; 50(27):6098-101. · 13.45 Impact Factor
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ABSTRACT: This study demonstrates the use of azobenzene-incorporated DNA as a control agent to precisely monitor three-dimensional DNA nanostructures. The shape of a DNA tetrahedron can be controlled by alternate irradiations with different wavelengths of light.
Chemical Communications 03/2011; 47(16):4670-2. · 6.17 Impact Factor
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ABSTRACT: This article is a review of the development and application of aptamer probes for cell imaging. Aptamers selected against whole cells have been modified with different fluorescent dyes and nanomaterials, such as gold nanoparticles, quantum dots, and superparamagnetic iron oxide, for their use as imaging probes of live cells. These probes have been successfully used for cell imaging both in vitro and in vivo by optical imaging, magnetic resonance imaging (MRI), computed tomography (CT), and positron-emission tomography (PET). In this article, we discuss the development of different aptamer-based probes currently available for imaging of live cells and their applications in the biomedical field.
Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology 03/2011; 3(3):328-40. · 5.19 Impact Factor
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ABSTRACT: The rational design of DNA/RNA aptamers for use as molecular probes depends on a clear understanding of their structural elements in relation to target-aptamer binding interactions. We present a simple method to create aptamer probes that can occupy two different structural states. Then, based on the difference in binding affinity between these states, target-aptamer binding interactions can be elucidated. The basis of our two-state system comes from the incorporation of azobenzene within the DNA strand. Azobenzene can be used to photoregulate the melting of DNA-duplex structures. When incorporated into aptamers, the light-regulated conformational change of azobenzene can be used to analyze how aptamer secondary structure is involved in target binding. Azobenzene-modified aptamers showed no change in target selectivity, but showed differences in binding affinity as a function of the number, position, and conformation of azobenzene modifications. Aptamer probes that can change binding affinity on demand may have future uses in targeted drug delivery and photodynamic therapy.
Bioconjugate Chemistry 02/2011; 22(2):282-8. · 4.93 Impact Factor
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ABSTRACT: An efficient pyrene-assisted method has been developed for the photolysis of disulfide bonds, with 77% of disulfides cleaved after only 20 min of irradiation (0.3W) at 350 nm. By employing a DNA framework, it was possible to observe both a distance-dependent cleavage pathway and a radical-forming photoreaction mechanism. To demonstrate the biomedical applications of such pyrene disulfide molecular assemblies, a DNA micelle structure and DNAzyme analog were further studied. Rapid photodriven disassembly of DNA micelles was achieved, allowing the further design of controlled pharmaceutical release at the target region and at a specific time. The DNAzyme analog can carry out multiple turnover reactions that follow the Michaelis-Menten equation, with a kcat of 10.2 min(-1) and a KM of 46.3 μM (0.3W 350 nm light source), comparable to that of common DNAzymes, e.g., 8-17 DNAzyme.
ACS Applied Materials & Interfaces 11/2010; 2(12):3601-5. · 4.53 Impact Factor
