Mingxu You

Assembly of Aptamer Switch Probes and Photosensitizer on Gold Nanorods for Targeted Photothermal and Photodynamic Cancer Therapy

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.

A Dual Platform for Selective Analyte Enrichment and Ionization in Mass Spectrometry Using Aptamer-Conjugated Graphene Oxide

This study demonstrates the use of aptamer-conjugated graphene oxide as an affinity extraction and detection platform for analytes from complex biological media. We have shown that cocaine and adenosine can be selectively enriched from plasma samples and that direct mass spectrometric readouts can be obtained without a matrix and with greatly improved signal-to-noise ratios. Aptamer-conjugated graphene oxide has clear advantages in target enrichment and in generating highly efficient ionization of target molecules for mass spectrometry. These results demonstrate the utility of the approach for analysis of small molecules in real biological samples.

Nanotechnology in Plant Disease Management: DNA-Directed Silver Nanoparticles on Graphene Oxide as an Antibacterial against Xanthomonas perforans

Bacterial spot caused by Xanthomonas perforans is a major disease of tomatoes, leading to reduction in production by 10-50%. While copper (Cu)-based bactericides have been used for disease management, most of the X. perforans strains isolated from tomatoes in Florida and other locations worldwide are Cu-resistant. We have developed DNA-directed silver (Ag) nanoparticles (NPs) grown on graphene oxide (GO). These Ag@dsDNA@GO composites effectively decrease X. perforans cell viability in culture and on plants. At the very low concentration of 16 ppm of Ag@dsDNA@GO, composites show excellent antibacterial capability in culture with significant advantages in improved stability, enhanced antibacterial activity, and stronger adsorption properties. Application of Ag@dsDNA@GO at 100 ppm on tomato transplants in a greenhouse experiment significantly reduced the severity of bacterial spot disease compared to untreated plants, giving results similar to those of the current grower standard treatment, with no phytotoxicity.

A Targeted, Self-delivered and Photocontrolled Molecular Beacon for mRNA Detection in Living Cells

The spatiotemporal dynamics of specific mRNA molecules are difficult to image and detect inside living cells, and this has been a significant challenge for the chemical and biomedical communities. To solve this problem, we have developed a targeted, self-delivered, and photocontrolled aptamer-based molecular beacon (MB) for intracellular mRNA analysis. An internalizing aptamer connected via a double-stranded DNA structure was used as a carrier probe (CP) for cell-specific delivery of the MB designed to signal target mRNA. A light activation strategy was employed by inserting two photolabile groups in the CP sequence, enabling control over the MBs intracellular function. After the probe was guided to the target cell via specific binding of aptamer AS1411 to nucleolin on the cell membrane, light illumination released the MB for mRNA monitoring. Consequently, the MB is able to perform live-cell mRNA imaging with precise spatiotemporal control, while the CP acts as both a tracer for intracellular distribution of the MB before photoinitiation and an internal reference for mRNA ratiometric detection.

Single-walled carbon nanotube as an effective quencher

Over the past few years, single-walled carbon nanotubes (SWNTs) have been the focus of intense research motivated by their unique physical and chemical properties. This review specifically summarizes recent progress in the development of fluorescence biosensors that integrate the quenching property of SWNTs and the recognition property of functional nucleic acids. SWNTs are substantially different from organic quenchers, showing superior quenching efficiency for a variety of fluorophores, with low background and high signal-to-noise ratio, as well as other advantages derived from the nanomaterial itself. As the second key component of biosensors, functional nucleic acids can bind to either their complementary DNA or a target molecule with the ability to recognize a broad range of targets from metal ions to organic molecules, proteins, and even live cells. By taking advantage of the strengths and properties of both SWNTs and nucleic acid based aptamers, a series of fluorescence biosensors have been designed and fabricated for the detection of a broad range of analytes with high selectivity and sensitivity.

An Autonomous and Controllable Light‐Driven DNA Walking Device

The development of nanotechnology has been largely inspired by the biological world. The complex, but well-organized, living system hosts an array of molecular-sized machines responsible for information processing, structure building and, sometimes, movement. We present here a novel light-powered DNA mechanical device, which is reminiscent of cellular protein motors in nature, especially those of green plants. This walking device, which is based on pyrene- assisted photolysis of disulfide bonds, is capable of autonomous locomotion, with light control of initiation, termination and velocity. Based on DNA sequence design and such physical conditions as temperature and ionic strength, this photon-fueled DNA walker exhibits the type of operational freedom and mechanical speed that may rival protein motors in the future.

DNA Micelle Flares for Intracellular mRNA Imaging and Gene Therapy

National Institutes of Health [GM066137, GM079359]; National Key Scientific Program of China [2011CB911000]; Foundation for Innovative Research Groups of NSFC [21221003]; China National Instrumentation Program [2011YQ03012412]

A Cell-Targeted, Size-Photocontrollable, Nuclear-Uptake Nanodrug Delivery System for Drug-Resistant Cancer Therapy

The development of multidrug resistance (MDR) has become an increasingly serious problem in cancer therapy. The cell-membrane overexpression of P-glycoprotein (P-gp), which can actively efflux various anticancer drugs from the cell, is a major mechanism of MDR. Nuclear-uptake nanodrug delivery systems, which enable intranuclear release of anticancer drugs, are expected to address this challenge by bypassing P-gp. However, before entering the nucleus, the nanocarrier must pass through the cell membrane, necessitating coordination between intracellular and intranuclear delivery. To accommodate this requirement, we have used DNA self-assembly to develop a nuclear-uptake nanodrug system carried by a cell-targeted near-infrared (NIR)-responsive nanotruck for drug-resistant cancer therapy. Via DNA hybridization, small drug-loaded gold nanoparticles (termed nanodrugs) can self-assemble onto the side face of a silver–gold nanorod (NR, termed nanotruck) whose end faces were modified with a cell type-specific internalizing aptamer. By using this size-photocontrollable nanodrug delivery system, anticancer drugs can be efficiently accumulated in the nuclei to effectively kill the cancer cells.

Photosensitizer-gold nanorod composite for targeted multimodal therapy.

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.

Programmable and Multiparameter DNA-Based Logic Platform For Cancer Recognition and Targeted Therapy

The specific inventory of molecules on diseased cell surfaces (e.g., cancer cells) provides clinicians an opportunity for accurate diagnosis and intervention. With the discovery of panels of cancer markers, carrying out analyses of multiple cell-surface markers is conceivable. As a trial to accomplish this, we have recently designed a DNA-based device that is capable of performing autonomous logic-based analysis of two or three cancer cell-surface markers. Combining the specific target-recognition properties of DNA aptamers with toehold-mediated strand displacement reactions, multicellular marker-based cancer analysis can be realized based on modular AND, OR, and NOT Boolean logic gates. Specifically, we report here a general approach for assembling these modular logic gates to execute programmable and higher-order profiling of multiple coexisting cell-surface markers, including several found on cancer cells, with the capacity to report a diagnostic signal and/or deliver targeted photodynamic therapy. The success of this strategy demonstrates the potential of DNA nanotechnology in facilitating targeted disease diagnosis and effective therapy.