Differentiating Reactive Oxygen Species with DNA Framework Monitors.

The lifespan, oxidizing properties, bonding behaviors, and reactivity of reactive oxygen species (ROS) produced during photocatalytic activation can vary significantly due to the differences in electron configurations of ROS, which are dependent on their generation mechanisms: energy transfer or charge transfer. Hence, identifying and differentiating ROS of different mechanisms can improve our understanding of redox reactions and related diseases, providing a basis for the prevention and treatment of related diseases. Here, we have developed a DNA framework monitor (DFM) based on dynamic DNA structural changes to effectively distinguish the two types of ROS produced in photocatalytic activation of O.

DNA Mechanics: From Single Stranded to Self-Assembled.

DNA encodes genetic information and forms various structural conformations with distinct physical, chemical, and biological properties. Over the past 30 years, advancements in force manipulation technology have enabled the precise manipulation of DNA at nanometer and piconewton resolutions. This mini-review discusses these force manipulation techniques for exploring the mechanical properties of DNA at the single-molecule level.

DNA Framework-Enabled 3D Organization of Antiarrhythmic Drugs for Radiofrequency Catheter Ablation.

Preorganizing molecular drugs within a microenvironment is crucial for the development of efficient and controllable therapeutic systems. Here, the use of tetrahedral DNA framework (TDF) is reported to preorganize antiarrhythmic drugs (herein doxorubicin, Dox) in 3D for catheter ablation, a minimally invasive treatment for fast heartbeats, aiming to address potential complications linked to collateral tissue damage and the post-ablation atrial fibrillation (AF) recurrence resulting from incomplete ablation. Dox preorganization within TDF transforms its random distribution into a confined, regular spatial arrangement governed by DNA.

Programmable Atom-Like Nanoparticle Reporters for High-Precision Urinalysis of In Situ Membrane Proteins.

The expression of disease-specific membrane proteins (MPs) is a crucial indicator for evaluating the onset and progression of diseases. Urinalysis of in situ MPs has the potential for point-of-care disease diagnostics, yet remains challenging due to the lack of molecular reporter to transform the expression information of in situ MPs into the measurable urine composition. Herein, a series of tetrahedral DNA frameworks (TDFs) are employed as the cores of programmable atom-like nanoparticles (PANs) to direct the self-assembly of PAN reporters with defined ligand valence and spatial distribution.

Morphology Dictated Immune Activation with Framework Nucleic Acids.

Framework nucleic acids (FNAs) of various morphologies, designed using the precise and programmable Watson-Crick base pairing, serve as carriers for biomolecule delivery in biology and biomedicine. However, the impact of their shape, size, concentration, and the spatial presentation of cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODNs) on immune activation remains incompletely understood. In this study, representative FNAs with varying morphologies are synthesized to explore their immunological responses.

Programing Immunogenic Cell Death in Breast Tumors with Designer DNA Frameworks.

The low response rate and serious side effects of cancer treatment pose significant limitations in immunotherapy. Here, we developed a multifunctional tetrahedral DNA framework (TDF) as a drug carrier to recruit chemotherapeutants and trigger immunogenic cell death (ICD) effects, which could turn tumors from cold to hot to boost the efficacy of antitumor immunotherapy. A tumor-targeting peptide RGD was modified on the TDF to increase the delivery efficiency, and the chemotherapeutant doxorubicin (DOX) was loaded to induce ICD effects, which were assisted by the immune adjuvant of CpG immunologic sequences linked on TDF.

Immunomodulation with Nucleic Acid Nanodevices.

The precise regulation of interactions of specific immunological components is crucial for controllable immunomodulation, yet it remains a great challenge. With the assistance of advanced computer design, programmable nucleic acid nanotechnology enables the customization of synthetic nucleic acid nanodevices with unprecedented geometrical and functional precision, which have shown promising potential for precise immunoengineering. Notably, the inherently immunologic functions of nucleic acids endow these nucleic acid-based assemblies with innate advantages in immunomodulatory engagement.

Sensing gastric cancer exosomes with MoS-based SERS aptasensor.

Exosomes have been widely used in early cancer diagnosis as promising cancer biomarkers due to their abundant tumor-specific molecular information. In this study, we developed a sensitive and straightforward surface-enhanced Raman scattering (SERS) aptasensor to detect exosomes based on gold nanostars-decorated molybdenum disulfide (MoS) nanocomposites (MoS-AuNSs). ROX-labeled aptamers (ROX-Apt) were assembled on MoS-AuNSs surface as recognition probes that specifically bind with transmembrane protein CD63 (a representative surface marker on exosomes).

Probing the self-assembly process of amphiphilic tetrahedral DNA frameworks.

Herein we utilized the thermal hysteresis method to directly probe the self-assembly process of amphiphilic DNA nanostructures, with the use of an amphiphilic tetrahedral DNA framework (am-TDF) as a model system. The analysis of the reaction rate surfaces under different ionic strengths revealed that strands of amphiphilic DNA first formed metastable micelles an entropy-driven process, which were then enthalpically transformed into am-TDF.

Molecular Visualization of Early-Stage Acute Kidney Injury with a DNA Framework Nanodevice.

DNA nanomachines with artificial intelligence have attracted great interest, which may open a new era of precision medicine. However, their in vivo behavior, including early diagnosis and therapeutic effect are limited by their targeting efficiency. Here, a tetrahedral DNA framework (TDF)-based nanodevice for in vivo near-infrared (NIR) diagnosis of early-stage AKI is developed.

Unbiased Enrichment of Circulating Tumor Cells Via DNAzyme-Catalyzed Proximal Protein Biotinylation.

Circulating tumor cells (CTCs) are noninvasive biomarkers with great potential for assessing neoplastic diseases. However, the enrichment bias toward heterogeneous CTCs remains to be minimized. Herein, a DNAzyme-catalyzed proximal protein biotinylation (DPPB) strategy is established for unbiased CTCs enrichment, employing DNA-framework-based, aptamer-coupled DNAzymes that bind to the surface marker of CTCs and subsequently biotinylated membrane proteins in situ.

Reconstructing Soma-Soma Synapse-like Vesicular Exocytosis with DNA Origami.

Cell-cell communications exhibit distinct physiological functions in immune responses and neurotransmitter signaling. Nevertheless, the ability to reconstruct a soma-soma synapse-like junction for probing intercellular communications remains difficult. In this work, we develop a DNA origami nanostructure-based method for establishing cell conjugation, which consequently facilitates the reconstruction of a soma-soma synapse-like junction.

Sequential Therapy of Acute Kidney Injury with a DNA Nanodevice.

The high demand for acute kidney injury (AKI) therapy calls the development of multifunctional nanomedicine for renal management with programmable pharmacokinetics. Here, we developed a renal-accumulating DNA nanodevice with exclusive kidney retention for longitudinal protection of AKI in different stages in a renal ischemia-reperfusion (I/R) model. Due to the prolonged kidney retention time (>12 h), the ROS-sensitive nucleic acids of the nanodevice could effectively alleviate oxidative stress by scavenging ROS in stage I, and then the anticomplement component 5a (aC5a) aptamer loaded nanodevice could sequentially suppress the inflammatory responses by blocking C5a in stage II, which is directly related to the cytokine storm.

Programming cell communications with pH-responsive DNA nanodevices.

DNA nanoswitches on cell surfaces could respond to changes of pH under physiological conditions by switching from a three-chain structure to a double-chain structure, thus connecting another set of cells modified with complementary single-stranded DNA. This pH-triggered cell communication offers a promising approach for cell-based therapy under a tumor microenvironment.

Responsive optical probes for deep-tissue imaging: Photoacoustics and second near-infrared fluorescence.

Optical imaging has played a vital role in development of biomedicine and image-guided theragnostic. Nevertheless, the clinical translation of optical molecular imaging for deep-tissue visualization is still limited by poor signal-to-background ratio and low penetration depth owing to light scattering and tissue autofluorescence. Hence, to facilitate precise diagnosis and accurate surgery excision in clinical practices, the responsive optical probes (ROPs) are broadly designed for specific reaction with biological analytes or disease biomarkers via chemical/physical interactions for photoacoustic and second near-infrared fluorescence (NIR-II, 900-1700 nm) fluorescence imaging.

Programming folding cooperativity of the dimeric i-motif with DNA frameworks for sensing small pH variations.

The response sensitivity of a molecular sensor is determined by the folding cooperativity of its responsive module. Using an H-responsive dimeric DNA i-motif as a model, we demonstrate the enhancement of its folding cooperativity through preorganization by a DNA framework, and with it we fabricate robust intracellular pH sensors with high response sensitivity.

Engineering Allosteric Ribozymes to Detect Thiamine Pyrophosphate in Whole Blood.

Thiamine deficiency contributes to several human diseases including Alzheimer's. As its biologically active form, thiamine pyrophosphate (TPP) has been considered as a potential biomarker for Alzheimer's disease (AD) based on several clinical reports that apparently lower blood TPP levels were found in patients with mild cognitive impairment to AD. However, highly sensitive and high-throughput detection of TPP in biological fluids remains an analytical challenge.

Programming CircLigase Catalysis for DNA Rings and Topologies.

Circular single-stranded (ss) DNA is an essential element in rolling circle amplification and many DNA nanotechnology constructions. It is commonly synthesized from linear ssDNA by a ligase, which nevertheless suffers from low and inconsistent efficiency due to the simultaneous formation of concatemeric byproducts. Here, we design an intramolecular terminal hybridization strategy to program the ring formation catalytic process of CircLigase, a thermostable RNA ligase 1 that can ligate ssDNA in an intramolecular fashion.

Encapsulation and release of living tumor cells using hydrogels with the hybridization chain reaction.

Circulating tumor cells (CTCs) enable noninvasive liquid biopsy and identification of cancer. Various approaches exist for the capture and release of CTCs, including microfluidic methods and those involving magnetic beads or nanostructured solid interfaces. However, the concomitant cell damage and fragmentation that often occur during capture make it difficult to extensively characterize and analyze living CTCs.

Ultrafast DNA Sensors with DNA Framework-Bridged Hybridization Reactions.

Intracellular DNA-based hybridization reactions generally occur under tension rather than in free states, which are spatiotemporally controlled in physiological conditions. However, how nanomechanical forces affect DNA hybridization efficiencies in in-vitro DNA assays, for example, biosensors or biochips, remains largely elusive. Here, we design DNA framework-based nanomechanical handles that can control the stretching states of DNA molecules.

Programming Cell-Cell Communications with Engineered Cell Origami Clusters.

Cells existing in the form of clusters often exhibit distinct physiological functions from their monodispersed forms, which have a close association with tissue and organ development, immunoresponses, and cancer metastasis. Nevertheless, the ability to construct artificial cell clusters as in vitro models for probing and manipulating intercellular communications remains limited. Here we design DNA origami nanostructure (DON)-based biomimetic membrane channels to organize cell origami clusters (COCs) with controlled geometric configuration and cell-cell communications.

DNA Nanoribbon-Templated Self-Assembly of Ultrasmall Fluorescent Copper Nanoclusters with Enhanced Luminescence.

Fluorescent copper nanoclusters (CuNCs) have been widely used in chemical sensors, biological imaging, and light-emitting devices. However, individual fluorescent CuNCs have limitations in their capabilities arising from poor photostability and weak emission intensities. As one kind of aggregation-induced emission luminogen (AIEgen), the formation of aggregates with high compactness and good order can efficiently improve the emission intensity, stability, and tunability of CuNCs.

DNA Origami-Enabled Engineering of Ligand-Drug Conjugates for Targeted Drug Delivery.

Effective drug delivery systems that can systematically and selectively transport payloads to disease cells remain a challenge. Here, a targeting ligand-modified DNA origami nanostructure (DON) as an antibody-drug conjugate (ADC)-like carrier for targeted prostate cancer therapy is reported. Specifically, DON of six helical bundles is modified with a ligand 2-[3-(1,3-dicarboxy propyl)-ureido] pentanedioic acid (DUPA) against prostate-specific membrane antigen (PSMA), to serve as the antibody for drug conjugation in ADC.

Treating Acute Kidney Injury with Antioxidative Black Phosphorus Nanosheets.

Black phosphorus nanosheets (BPNSs) have been actively employed as nanomedicine agents for photothermal and photodynamic therapy by virtue of their unique optical properties. However, their chemical reactivity as a competent biomaterial has not been fully explored yet. Here, we report on the use of BPNSs as reactive oxygen species (ROS) scavengers to cure acute kidney injury (AKI) in mice.

DNA Framework-Programmed Micronano Hierarchy Sensor Interface for Metabolite Analysis in Whole Blood.

A microsubstrate is of great value for constructing a microscale interface with highly improved sensing capabilities. What has been lacking, however, is the precisely nanoscale regulation of the probes that anchored on the interface of the microsubstrate. Here we employed tetrahedron DNA framework (TDF) to program the microscale biosensing interface for metabolite analysis.