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Multivalent interactions of biomolecules play pivotal roles in physiological and pathological settings. Whereas the directionality of the interactions is crucial, the state‐of‐the‐art synthetic multivalent ligand–receptor systems generally lack programmable approaches for orthogonal directionality. Here, we report the design of programmable atom‐like nanoparticles (aptPANs) to direct multivalent aptamer–receptor binding on the cell interface. The positions of the aptamer motifs can be prescribed on tetrahedral DNA frameworks to realize atom‐like orthogonal valence and direction, enabling the construction of multivalent molecules with fixed aptamer copy numbers but different directionality. These directional‐yet‐flexible aptPAN molecules exhibit the adaptability to the receptor distribution on cell surfaces. We demonstrate the high‐affinity tumor cell binding with a linear aptPAN oligomer (≈13‐fold improved compared to free aptamers), which leads to ≈50 % suppression of cell growth. [ABSTRACT FROM AUTHOR]

Advances in bioimaging technologies have led to unprecedented findings of novel biological processes at the nanoscale. However, there remains an ever-lasting demand for the improvement of spatiotemporal resolution, multiplexity, and smart responsiveness of bioimaging in living systems. In recent decades, self-assembled DNA nanostructures with highly programmable shape, nanometer addressability, and structural responsiveness have shown great promise in developing nanoscale probes and labels for high-performance bioimaging. Here, we briefly review the recent progress in structural DNA nanotechnology and the development of DNA frameworks, and summarize the bioimaging strategies empowered by DNA nanotechnology. We highlight the advantages of DNA nanostructures in overcoming the bottlenecks in bioimaging and discuss the challenges and opportunities in this field. [ABSTRACT FROM AUTHOR]

Abstract: Weak ligand–receptor recognition events are often amplified by recruiting multiple regulatory biomolecules to the action site in biological systems. However, signal amplification in in vitro biomimetic systems generally lack the spatiotemporal regulation in vivo. Herein we report a framework nucleic acid (FNA)‐programmed strategy to develop valence‐controlled signal amplifiers with high modularity for ultrasensitive biosensing. We demonstrated that the FNA‐programmed signal amplifiers could recruit nucleic acids, proteins, and inorganic nanoparticles in a stoichiometric manner. The valence‐controlled signal amplifier enhanced the quantification ability of electrochemical biosensors, and enabled ultrasensitive detection of tumor‐relevant circulating free DNA (cfDNA) with sensitivity enhancement of 3–5 orders of magnitude and improved dynamic range. [ABSTRACT FROM AUTHOR]

Microarrays of biomolecules hold great promise in the fields of genomics, proteomics, and clinical assays on account of their remarkably parallel and high-throughput assay capability. However, the fluorescence detection used in most conventional DNA microarrays is still limited by sensitivity. In this study, we have demonstrated a novel universal and highly sensitive platform for fluorescent detection of sequence specific DNA at the femtomolar level by combining dextran-coated microarrays with hybridization chain reaction (HCR) signal amplification. Three-dimensional dextran matrix was covalently coated on glass surface as the scaffold to immobilize DNA recognition probes to increase the surface binding capacity and accessibility. DNA nanowire tentacles were formed on the matrix surface for efficient signal amplification by capturing multiple fluorescent molecules in a highly ordered way. By quantifying microscopic fluorescent signals, the synergetic effects of dextran and HCR greatly improved sensitivity of DNA microarrays, with a detection limit of 10 fM (1×10 5 molecules). This detection assay could recognize one-base mismatch with fluorescence signals dropped down to ~20%. This cost-effective microarray platform also worked well with samples in serum and thus shows great potential for clinical diagnosis. [ABSTRACT FROM AUTHOR]