Dannong He

Hybridization Chain Reaction Amplification of MicroRNA Detection with a Tetrahedral DNA Nanostructure-Based Electrochemical Biosensor

There remains a great challenge in the sensitive detection of microRNA because of the short length and low abundance of microRNAs in cells. Here, we have demonstrated an ultrasensitive detection platform for microRNA by combining the tetrahedral DNA nanostructure probes and hybridization chain reaction (HCR) amplification. The detection limits for DNA and microRNA are 100 aM and 10 aM (corresponding to 600 microRNAs in a 100 μL sample), respectively. Compared to the widely used supersandwich amplification, the detection limits are improved by 3 orders of magnitude. The uncontrolled surface immobilization and consumption of target molecules that limit the amplification efficiency of supersandwich are eliminated in our platform. Taking advantage of DNA nanotechnology, we employed three-dimensional tetrahedral DNA nanostructure as the scaffold to immobilize DNA recognition probes to increase the reactivity and accessibility, while DNA nanowire tentacles are used for efficient signal amplification by capturing multiple catalytic enzymes in a highly ordered way. The synergetic effect of DNA tetrahedron and nanowire tentacles have proven to greatly improve sensitivity for both DNA and microRNA detection.

Uniform Ultrasmall Graphene Oxide Nanosheets with Low Cytotoxicity and High Cellular Uptake

Graphene oxide (GO) is an increasingly important nanomaterial, which exhibits great promise in the area of bionanotechnology and nanobiomedicine. In this study, we synthesized uniform ultrasmall graphene oxide nanosheets with high yield by a convenient way of modified Hummers method. The uniform ultrasmall GO nanosheets, which exhibit fluorescence property and outstanding stability in a wide range of pH values, were less than 50 nm. Furthermore, because of the advantages of its lateral size, the uniform ultrasmall GO nanosheets showed excellent biocompatibility of lower cytotoxicity and higher cellular uptake amount compared to the random large GO nanosheets. Therefore, the as-prepared uniform ultrasmall GO nanosheets could be explored as the ideal nanocarriers for drug delivery and intracellular fluorescent nanoprobe.

Molecular Logic Gates on DNA Origami Nanostructures for MicroRNA Diagnostics

Molecular computing holds great promise for diagnosis and treatment of diseases at the molecular level; nevertheless, designing molecular logic gates to operate programmably and autonomously for molecular diagnostics still remains challenging. We designed logic gates on DNA Origami for microRNA analysis. As a demonstration, two indicators of heart failure, microRNA-21 and microRNA-195, were selected as the logic inputs. The logic gates contain two main modules: computation module and output module, performing in a single DNA Origami nanostructure. The computation module recognizes disease indicators, while the output module display different nanoscale symbols, + (positive) or - (negative), depending on the computing results. We demonstrated that the molecular logic gates worked well with single and two input combinations.

3D Artificial Bones for Bone Repair Prepared by Computed Tomography-Guided Fused Deposition Modeling for Bone Repair

The medical community has expressed significant interest in the development of new types of artificial bones that mimic natural bones. In this study, computed tomography (CT)-guided fused deposition modeling (FDM) was employed to fabricate polycaprolactone (PCL)/hydroxyapatite (HA) and PCL 3D artificial bones to mimic natural goat femurs. The in vitro mechanical properties, in vitro cell biocompatibility, and in vivo performance of the artificial bones in a long load-bearing goat femur bone segmental defect model were studied. All of the results indicate that CT-guided FDM is a simple, convenient, relatively low-cost method that is suitable for fabricating natural bonelike artificial bones. Moreover, PCL/HA 3D artificial bones prepared by CT-guided FDM have more close mechanics to natural bone, good in vitro cell biocompatibility, biodegradation ability, and appropriate in vivo new bone formation ability. Therefore, PCL/HA 3D artificial bones could be potentially be of use in the treatment of patients with clinical bone defects.

Growth and Origami Folding of DNA on Nanoparticles for High-Efficiency Molecular Transport in Cellular Imaging and Drug Delivery

A novel three-dimensional (3D) superstructure based on the growth and origami folding of DNA on gold nanoparticles (AuNPs) was developed. The 3D superstructure contains a nanoparticle core and dozens of two-dimensional DNA belts folded from long single-stranded DNAs grown inu2005situ on the nanoparticle by rolling circle amplification (RCA). We designed two mechanisms to achieve the loading of molecules onto the 3D superstructures. In one mechanism, ligands bound to target molecules are merged into the growing DNA during the RCA process (merging mechanism). In the other mechanism, target molecules are intercalated into the double-stranded DNAs produced by origami folding (intercalating mechanism). We demonstrated that the as-fabricated 3D superstructures have a high molecule-loading capacity and that they enable the high-efficiency transport of signal reporters and drugs for cellular imaging and drug delivery, respectively.

Phase and morphological transitions of titania/titanate nanostructures from an acid to an alkali hydrothermal environment†

A systematical investigation was established to uncover the phase transition of titania/titanate nanostructures in acidic and alkaline media. X-ray diffraction was used to identify the phase composition and phase transition behavior, and field emission scanning electron microscopy was employed to elucidate the morphological transitions of the titania/titanate products, which resulted in the determination of a phase and morphological transition diagram of titania/titanate nanostructures in connection with the acid/alkali concentrations. The crystal growth of rutile nanorods and anatase nanoparticles was proposed following Ostwalds ripening mechanism, but crystal growth of brookite and titanate products should follow another formation mechanism according to Ostwalds step rule, which reveals the phase transitions from layered structure to brookite, dititanate or trititanate under hydrothermal treatment. The anatase samples and anatase–rutile composite obtained in 0.1 M HCl exhibited excellent photocatalytic activities in the photodegradation experiments of methyl orange, salicylic acid and phenol solution under UV irradiation.

A power-free microfluidic chip for SNP genotyping using graphene oxide and a DNA intercalating dye

We herein report a power-free microfluidic chip for fluorescent DNA detection with high single-nucleotide polymorphism discrimination, using a DNA intercalator and graphene oxide.

Carbon nanotubes multifunctionalized by rolling circle amplification and their application for highly sensitive detection of cancer markers.

There are still challenges for the development of multifunctional carbon nanotubes (CNTs). Here, a multiwalled carbon nanotube (MWCNT)-based rolling circle amplification system (CRCAS) is reported which allows in situ rolling circle replication of DNA primer on the surface of MWCNTs to create a long single-strand DNA (ssDNA) where a large number of nanoparticles or proteins could be loaded, forming a nano-biohybridized 3D structure with a powerful signal amplification ability. In this strategy, the binding ability of proteins, hybridization, replication ability of DNA, and the catalytical ability of enzymes are integrated on a single carbon nanotube. The CRCAS is then used to develop colorimetric and chemiluminescent assays for the highly sensitive and specific detection of cancer protein markers, alpha-fetoprotein (AFP) and prostate specific antigen (PSA). The colorimetric CRCAS assay is 4000 times more sensitive than a conventional enzyme-linked immunosorbent assay (ELISA), and its concentration range is 10,000 times wider. Control experiments show that as low as 10 pg mL⁻¹ AFP or PSA could be detected even in the presence of interfering protein markers with a more than 10⁵-fold greater concentration in the sample, demonstrating the high specificity of the CRCAS assay. The limit of detection of the chemiluminescent CRCAS assays for AFP and PSA are 5 fg mL⁻¹ (70 aM) and 10 fg mL⁻¹ (0.29 fM), respectively, indicating that the sensitivity is much higher than that of the colorimetric CRCAS assay. Importantly, CRCAS works well with real biological samples.

Long-Term Effects of Nanoparticles on Nutrition and Metabolism

Nanoparticles have shown great potential in biological and biomedical applications due to their distinct physical and chemical properties. In the meanwhile, the biosafety of nanoparticles has also raised intense concerns worldwide. To address such concerns, great efforts have been made to examine short-term effects of nanoparticles on cell survival and proliferation. More recently, exploration of long-term effects of nanomaterials, particularly those with promising biomedical applications in vivo, has aroused significant interest. For example, gold nanoparticles (AuNPs) are generally considered non-toxic to cell growth, whereas recent studies suggest that AuNPs might have long-term effects on cellular metabolism and energy homeostasis. In this Review, recent advances in this direction are summarized. Further, possible mechanisms under which nanoparticles regulate metabolic signaling pathways, potential long-term effects on cellular anabolic or catabolic processes, and their implications in human health and metabolic disorders are discussed.

Tip-induced micropatterning of silk fibroin protein using in situ solution atomic force microscopy.

Silk fibroin (SF) is a promising candidate for a variety of application in the fields of tissue engineering, drug delivery, and biomedical optics. Recent research has already begun to explore the construction of nano- and micropatterned SF films under ambient environment. The structure and biocompatibility of SF are dependent on SF state (solution or solid) and the method of drying the SF solution to prepare various biomaterials such as films, sponges, and fibers. Therefore, it is important to explore the construction of SF nano- and micropatterns under aqueous solution. This paper reports a novel application of atomic force microscopy (AFM) under liquid for direct deposition of the relatively hydrophobic protein SF onto hydrophilic mica. We demonstrate that the AFM tip, in either the contact or the tapping mode, can fabricate SF micropatterns on mica with controlled surface topography. We show that the deposition process requires a mechanical force-induced SF sol-gel transition followed by a transfer to the mica surface at the tip-surface contact, and the efficiency of this process depends on not only AFM operation mode but also the SF bulk concentration, the SF amount on mica, and the AFM tip spring constant.