Cells interact with the extracellular environment through molecules expressed on the membrane. Disruption of these membrane-bound interactions (or encounters) can result in disease progression. Advances in super-resolution microscopy have allowed membrane encounters to be examined, however, these methods cannot image entire membranes and cannot provide information on the dynamic interactions between membrane-bound molecules. Here, we show a novel DNA probe that can transduce transient membrane encounter events into readable cumulative fluorescence signals. The probe, which translocates from one anchor site to another, such as motor proteins, is realized through a toehold-mediated DNA strand displacement reaction. Using this probe, we successfully monitored rapid encounter events of membrane lipid domains using flow cytometry and fluorescence microscopy. Our results show a preference for encounters within different lipid domains.

Cell types, both healthy and diseased, can be classified by inventories of their cell-surface markers. Programmable analysis of multiple markers would enable clinicians to develop a comprehensive disease profile, leading to more accurate diagnosis and intervention. As a first step to accomplish this, we have designed a DNA-based device, called “Nano-Claw”. Combining the special structure-switching properties of DNA aptamers with toehold-mediated strand displacement reactions, this claw is capable of performing autonomous logic-based analysis of multiple cancer cell-surface markers and, in response, producing a diagnostic signal and/or targeted photodynamic therapy. We anticipate that this design can be widely applied in facilitating basic biomedical research, accurate disease diagnosis and effective therapy.

The ability to self-assemble one-dimensional DNA building blocks into two- and three-dimensional nanostructures via DNA/RNA nanotechnology has led to broad applications in bioimaging, basic biological mechanism studies, disease diagnosis and drug delivery. However, the cellular uptake of most nucleic acid nanostructures is dependent on passive delivery or the enhanced permeability and retention effect, which may not be suitable for certain types of cancers, especially for treatment in vivo. To meet this need, we have constructed a multifunctional aptamer-based DNA nanoassembly (AptNA) for targeted cancer therapy. In particular, we first designed various Y-shaped functional DNA domains through predesigned base pair hybridization, including targeting aptamers, intercalated anticancer drugs and therapeutic antisense oligonucleotides. Then these functional DNA domains were linked to an X-shaped DNA core connector, termed a building unit, through the complementary sequences in the arms of functional domains and connector. Finally, hundreds (~100–200) of these basic building units with 5′-modification of acrydite groups were further photocrosslinked into a multifunctional and programmable aptamer-based nanoassembly structure able to take advantage of facile modular design and assembly, high programmability, excellent biostability and biocompatibility, as well as selective recognition and transportation. With these properties, AptNAs were demonstrated to have specific cytotoxic effect against leukemia cells. Moreover, the incorporation of therapeutic antisense oligonucleotides resulted in the inhibition of P-gp expression (a drug efflux pump to increase excretion of anticancer drugs), as well as a decrease in drug resistance. Therefore, these multifunctional and programmable aptamer-based DNA nanoassemblies show promise as candidates for targeted drug delivery and cancer therapy.

We have developed a photoresponsive DNA-crosslinked hydrogel which can be photoregulated by two wavelengths with a reversible sol-gel conversion. This photoinduced conversion can be further untilized for precisely controllable encapsulation and release of multiple loads. Specifically, photosensitive azobenzene moieties are incorporated into DNA strands as crosslinkers, such that their hybridization to complementary DNAs responds differently to different wavelengths of light. Based on the rhyology variation of hydrogels, it is possible to utilize this material for storing and releasing molecules and nanoparticles. To prove the concept, three different materials, fluorescein, horseradish peroxidase and gold nanoparticles, were encapsulated inside the gel at 450 nm and then released by photons at 350 nm. Further experiments were carried out to deliver the chemotherapy drug doxorubicin in a similar manner in vitro. Our results show a net release rate of 65% within 10 minutes, and the released drug maintained its therapeutic effect. This hydrogel system provides a promising platform for drug delivery in targeted therapy and in biotechnological applications.

Organic dye based NIR‐II fluorescent probes, owing to their high signal‐to‐background ratio and deeper penetration, are highly useful for deep‐tissue high‐contrast imaging in vivo. However, it is still a challenge to design activatable NIR‐II fluorescent probes. Here, a novel class of polymethine dyes (NIRII‐RTs), with bright (quantum yield up to 2.03 %), stable, and anti‐solvent quenching NIR‐II emission, together with large Stokes shifts, was designed. Significantly, the novel NIR‐II dyes NIRII‐RT3 and NIRII‐RT4, equipped with a carboxylic acid group, can serve as effective NIR‐II platforms for the design of activatable bioimaging probes with high contrast. As a proof of concept, a series of target‐activatable NIRII‐RT probes (NIRII‐RT‐pH, NIRII‐RT‐ATP and NIRII‐RT‐Hg) for pH, adenosine triphosphate (ATP), and metal‐ion detection, were synthesized. By applying the NIRII‐RT probe, the real‐time monitoring of drug‐induced hepatotoxicity was realized.

Fiber‐shaped micro‐supercapacitors (micro‐SCs) have attracted enormous interest in wearable electronics due to high flexibility and weavability. However, they usually present a low energy density because of inhomogeneity and less pores. Here, we demonstrate a microfluidic‐directed strategy to synthesize homogeneous nitrogen‐doped porous graphene fibers. The porous fibers‐based micro‐SCs utilize solid‐state phosphoric acid/polyvinyl alcohol (H3PO4/PVA) and 1‐ethyl‐3‐methylimidazolium tetrafluoroborate/poly(vinylidenefluoride‐co‐hexafluoropropylene) (EMIBF4/PVDF‐HFP) electrolytes, which show significant improvements in electrochemical performances. Ultralarge capacitance (1132 mF cm−2), high cycling‐stability, and long‐term bending‐durability are achieved based on H3PO4/PVA. Additionally, high energy densities of 95.7–46.9 µWh cm−2 at power densities of 1.5–15 W cm−2 are obtained in EMIBF4/PVDF‐HFP. The key to higher performances stems from microfluidic‐controlled fibers with a uniformly porous network, large specific surface area (388.6 m2 g−1), optimal pyridinic nitrogen (2.44%), and high electric conductivity (30785 S m−1) for faster ion diffusion and flooding accommodation. By taking advantage of these remarkable merits, this study integrates micro‐SCs into flexible and fabric substrates to power audio–visual electronics. The main aim is to clarify the important role of microfluidic techniques toward the architecture of electrodes and promote development of wearable electronics.

Molecular recognition is fundamental to the specific interactions between molecules, of which the best known examples are antibody-antigen binding and complementary DNA 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 collection of changes at the molecular level to provide macroscopic observables. This research makes use of photo-responsive molecular recognition for the fabrication of novel photo-regulated dynamic materials. Specifically, a dynamic hydrogel was prepared by grafting azobenzene-tethered ssDNA and its complementary DNA to the hydrogel network. The macroscopic volume of the hydrogel can be manipulated through the photo-reversible DNA hybridization controlled by alternating irradiation of UV and visible light. The effects of synthetic parameters including the concentration of DNA, polymer monomer and permanent crosslinker are also discussed.

Researchers increasingly envision an important role for artificial biochemical circuits in biological engineering, much like electrical circuits in electrical engineering. Similar to electrical circuits, which control electromechanical devices, biochemical circuits could be utilized as a type of servomechanism to control nanodevices in vitro, monitor chemical reactions in situ, or regulate gene expressions in vivo.1 As a consequence of their relative robustness and potential applicability for controlling a wide range of in vitro chemistries, synthetic cell-free biochemical circuits promise to be useful in manipulating the functions of biological molecules. Here we describe the first logical circuit based on DNA-protein interactions with accurate threshold control, enabling autonomous, self-sustained and programmable manipulation of protein activity in vitro. Similar circuits made previously were based primarily on DNA hybridization and strand displacement reactions. This new design uses the diverse nucleic acid interactions with proteins. The circuit can precisely sense the local enzymatic environment, such as the concentration of thrombin, and when it is excessively high, a coagulation inhibitor is automatically released by a concentration-adjusted circuit module. To demonstrate the programmable and autonomous modulation, a molecular circuit with different threshold concentrations of thrombin was tested as a proof of principle. In the future, owing to tunable regulation, design modularity and target specificity, this prototype could lead to the development of novel DNA biochemical circuits to control the delivery of aptamer-based drugs in smart and personalized medicine, providing a more efficient and safer therapeutic strategy.