Innate immune cells in tumor microenvironment: A new frontier in cancer immunotherapy.

Innate immune cells, crucial in resisting infections and initiating adaptive immunity, play diverse and significant roles in tumor development. These cells, including macrophages, granulocytes, dendritic cells (DCs), innate lymphoid cells, and innate-like T cells, are pivotal in the tumor microenvironment (TME). Innate immune cells are crucial components of the TME, based on which various immunotherapy strategies have been explored.

Self-assembly of DNA G-quadruplex nanowires: a study of the mechanism towards micrometer length.

The G-quadruplex (GQ) formed by guanine-rich DNA strands exhibits superior thermal stability and electric properties, which have generated substantial interest in applying GQ DNA to bioelectric interfaces. However, single G-wires formed by GQs have not yet surpassed the μm length due to the lack of an optimal assembly protocol and understanding of assembly mechanisms that limit application. Herein, we optimized a self-assembly protocol for a short 4-nt oligonucleotide (dG4) to achieve micrometer lengths of G-wires, including the buffer composition, incubation process and surface assembly.

Silencing circATXN1 in Aging Nucleus Pulposus Cell Alleviates Intervertebral Disc Degeneration via Correcting Progerin Mislocalization.

Circular RNAs (circRNAs) play a critical regulatory role in degenerative diseases; however, their functions and therapeutic applications in intervertebral disc degeneration (IVDD) have not been explored. Here, we identified that a novel circATXN1 highly accumulates in aging nucleus pulposus cells (NPCs) accountable for IVDD. CircATXN1 accelerates cellular senescence, disrupts extracellular matrix organization, and inhibits mitochondrial respiration.

A redox-activated Pt(IV) pro-probe: From G-quadruplex imaging to cancer therapy.

Efficient uptake to both cytoplasm and nucleus in live cells remains a key obstacle for G-quadruplex targeting fluorophores. We developed a Pt(IV) complex by oxidizing a bisphenanthrolinyl Pt(II) complex, which is our first generation G-quadruplex specific fluorogenic probe. The axial lipophilic ligand assists Pt(IV) pro-probe to enter live cells and reach the nucleus rapidly.

Metallointercalators-DNA Tetrahedron Supramolecular Self-Assemblies with Increased Serum Stability.

Self-assembly of metallointercalators into DNA nanocages is a rapid and facile approach to synthesize discrete bioinorganic host/guest structures with a high load of metal complexes. Turberfield's DNA tetrahedron can accommodate one intercalator for every two base pairs, which corresponds to 48 metallointercalators per DNA tetrahedron. The affinity of the metallointercalator for the DNA tetrahedron is a function of both the structure of the intercalating ligand and the overall charge of the complex, with a trend in affinity [Ru(bpy)(dppz)] > [Tb-DOTAm-Phen] ≫ Tb-DOTA-Phen.

Rapid enrichment and sensitive detection of extracellular vesicles through measuring the phospholipids and transmembrane protein in a microfluidic chip.

Extracellular vesicles (EVs) have attracted tremendous attention in recent years and quantification of EVs is a key issue in the evaluation of vesicle-based diagnostics and therapeutic development, but it's quite challenging to determine whether higher protein expression signals are due to larger vesicle amount or higher protein content within each vesicle. To solve this problem, herein, we proposed a strategy based on staining phospholipid bilayers of EVs with lipophilic dyes to evaluate their lipid amount, which was subsequently normalized as an internal standard for studying the expression of transmembrane protein (i.e.

Self-Assembly of Dendritic DNA into a Hydrogel: Application in Three-Dimensional Cell Culture.

With inherent biocompatibility, biodegradability, and unique programmability, hydrogels with a DNA framework show great potential in three-dimensional (3D) cell culture. Here, a DNA hydrogel was assembled by a dendritic DNA with four branches. The hydrogel showed tunable mechanical strength and reversible thixotropy even under a nanomolar DNA concentration.

Simultaneous RNA-DNA FISH.

A highly useful tool for studying lncRNAs is simultaneous RNA-DNA FISH, which reveals the localization and quantitative information of RNA and DNA in cellular contexts. However, a simple combination of RNA FISH and DNA FISH often generates disappointing results because the fragile RNA signals are often damaged by the harsh conditions used in DNA FISH for denaturing the DNA. Here, we describe a robust and simple RNA-DNA FISH protocol, in which amino-labeled nucleic acid probes are used for RNA FISH .

Fluorogenic Pt complexes distinguish the quantity and folding behavior of RNA G-quadruplexes between live cancerous and healthy cells.

Two Pt complexes with high quantum yields and photostability, and low cytotoxicity, were developed to track RNA G-quadruplexes (GQs) in live cells. Higher number and intensity, and longer lifetime of fluorescent foci in cancer cells than those in healthy cells suggest that the quantity and folding dynamics of RNA GQs could not only correlate to their biological functions, but be two novel biomarkers to characterize cancerous cells.

Graphene Quantum Dot-Based Nanocomposites for Diagnosing Cancer Biomarker APE1 in Living Cells.

As an essential DNA repair enzyme, apurinic/apyrimidinic endonuclease 1 (APE1) is overexpressed in most human cancers and is identified as a cancer diagnostic and predictive biomarker for cancer risk assessment, diagnosis, prognosis, and prediction of treatment efficacy. Despite its importance in cancer, however, it is still a significant challenge nowadays to sense abundance variation and monitor enzymatic activity of this biomarker in living cells. Here, we report our construction of biocompatible functional nanocomposites, which are a combination of meticulously designed unimolecular DNA and fine-sized graphene quantum dots.

One-Dimensional Assemblies of a DNA Tetrahedron: Manipulations on the Structural Conformation and Single-Molecule Behaviors.

DNA nanotechnology can construct various nanostructures with diverse functionalities. However, conformation fluctuations due to the structural flexibility of duplex DNA compromise the efficiency to realize the functionality and reactivity of DNA nanostructures. To understand and control the structural deviation from the design represents a major challenge as well as an opportunity for DNA nanotechnology.

Versatile Types of DNA-Based Nanobiosensors for Specific Detection of Cancer Biomarker FEN1 in Living Cells and Cell-Free Systems.

Flap structure-specific endonuclease 1 (FEN1) is overexpressed in various types of human cancer cells and has been recognized as a promising biomarker for cancer diagnosis in the recent years. In order to specifically detect the abundance and activity of this cancer-overexpressed enzyme, different types of DNA-based nanodevices were created during our investigations. It is shown in our studies that these newly designed biosensors are highly sensitive and specific for FEN1 in living cells as well as in cell-free systems.

Reversible Thermal Cycling of DNA Material for Efficient Cellulose Hydrolysis.

Enzymatic catalysis on the insoluble substrates commonly suffers from low enzyme stability, catalytic activity, and product recovery. Herein, a "thermal cycling method" of DNA material is proposed to tackle the challenges in enzymatic reaction, in which a thermal responsive self-assembled DNA material is designed for enzyme recovery. We demonstrate the remarkable advantages of this new method in cellulosic hydrolysis.

G-quadruplex Nanowires To Direct the Efficiency and Selectivity of Electrocatalytic CO Reduction.

DNA as a medium for electron transfer has been widely used in photolytic processes but is seldom applied to dark reaction of CO reduction. A G-quadruplex nanowire (tsGQwire) assembled by guanine tetranucleotides was used to host several metal complexes and further to mediate electron transfer processes in the electrochemical reduction of CO catalyzed by these complexes. The tsGQwire modified electrode increased the Faradaic efficiency of cobalt(II) phthalocyanine (Co Pc) 2.

A Molecular Dynamics-Quantum Mechanics Theoretical Study of DNA-Mediated Charge Transport in Hydrated Ionic Liquids.

Charge transport (CT) through biomolecules is of high significance in the research fields of biology, nanotechnology, and molecular devices. Inspired by our previous work that showed the binding of ionic liquid (IL) facilitated charge transport in duplex DNA, in silico simulation is a useful means to understand the microscopic mechanism of the facilitation phenomenon. Here molecular dynamics simulations (MD) of duplex DNA in water and hydrated ionic liquids were employed to explore the helical parameters.

Sulfinate Based Selective Labeling of 5-Hydroxymethylcytosine: Application to Biotin Pull Down Assay.

We developed an enzyme-free, chemical method to selectively label the epigenetic base, 5-hydroxymethylcytosine (hmC) with versatile sulfinate reagents in aqueous solvent under mild reaction conditions. This method allows efficient single step conjugation of biotin to hmC site in DNA for enrichment and pull down assays.

Dual functional dinuclear platinum complex with selective reactivity towards c-myc G-quadruplex.

G-quadruplexes (GQ) folded by the oncogenic G-rich sequences are the promising targets for developing anticancer therapeutic molecules. However, the current drug development mainly focused on non-covalent dynamic binders to stabilize GQ structures, while the covalent targeting from inorganic complexes via chelating principles, as a potent therapeutic strategy was surprisingly lack of exploration. Herein, a series of dinuclear platinum complexes, [(Pt(Dip)Cl)(μ-diamine)](NO) (Dip: 4,7-diphenyl-1,10-phenanthroline), were designed to contain two dual-functional Pt cores connected by an alkyl linkage.

Fabrication of circular assemblies with DNA tetrahedrons: from static structures to a dynamic rotary motor.

DNA tetrahedron as the simplest 3D DNA nanostructure has been applied widely in biomedicine and biosensing. Herein, we design and fabricate a series of circular assemblies of DNA tetrahedron with high purity and decent yields. These circular nanostructures are confirmed by endonuclease digestion, gel electrophoresis and atomic force microscopy.

Efficient Long-Range Hole Transport Through G-Quadruplexes.

DNA offers a means of long-range charge transport for biology and electric nanodevices. Here, a series of tetra-stranded G-quadruplexes were assembled within a dendritic DNA architecture to explore oxidative charge transport (hole transport) through the G-quadruplex. Efficient charge transport was achieved over 28 Å upon UV irradiation.

Ultrathin Two-Dimensional Covalent Organic Framework Nanosheets: Preparation and Application in Highly Sensitive and Selective DNA Detection.

The ability to prepare ultrathin two-dimensional (2D) covalent organic framework (COF) nanosheets (NSs) in high yield is of great importance for the further exploration of their unique properties and potential applications. Herein, by elaborately designing and choosing two flexible molecules with C molecular symmetry as building units, a novel imine-linked COF, namely, TPA-COF, with a hexagonal layered structure and sheet-like morphology, is synthesized. Since the flexible building units are integrated into the COF skeletons, the interlayer stacking becomes weak, resulting in the easy exfoliation of TPA-COF into ultrathin 2D NSs.

Hole Transport in A-form DNA/RNA Hybrid Duplexes.

DNA/RNA hybrid duplexes are prevalent in many cellular functions and are an attractive target form for electrochemical biosensing and electric nanodevice. However the electronic conductivities of DNA/RNA hybrid duplex remain relatively unexplored and limited further technological applications. Here cyclopropyl-modified deoxyribose- and ribose-adenosines were developed to explore hole transport (HT) in both DNA duplex and DNA/RNA hybrids by probing the transient hole occupancies on adenine tracts.

Aza-bridged bisphenanthrolinyl Pt(II) complexes: Efficient stabilization and topological selectivity on telomeric G-quadruplexes.

Two platinum complexes with an aza-bridged bis(1,10-phenanthrolin-2-yl)amine (bpa) were synthesized. The two phenanthrolines in bpa entered a flat plane prior to binding of nucleic acids, which bestowed on the two Pt complexes a significantly high stabilizing ability on both DNA and RNA G-quadruplexes. Further extending alkyl tail from aromatic coordination core enabled the complexes to distinguish GQ sequence based upon the topological folding structures and enhanced the selectivity of the complex against duplex DNA.