Site-specific bioorthogonal regulation of bone morphogenetic protein 2 expression for effective bone regeneration.

Growth factor holds great promise for bone regeneration, and spatiotemporal control of their expressing through site-specific reactions is crucial but challenging for on-demand therapy. In this study, we present the development of a novel unnatural amino acids (UAAs)-triggered therapeutic switch (UATS) system, composed of an orthogonal aminoacyl-tRNA-synthase (aaRS)-tRNA pair and a bone morphogenetic protein 2 (BMP2) gene harboring premature stop codon, which enable in situ and on-demand initiation of the expression of BMP2. The resulting UATS system allowed specifically control of base expressing on the BMP2 mRNA that switched to the BMP2 protein with complete structure and function to facilitate bone regeneration.

Fc receptor-like A promotes malignant behavior in renal cell carcinoma and correlates with tumor immune infiltration.

Background: Our study aims to investigate the mechanisms through which Fc receptor-like A (FCRLA) promotes renal cell carcinoma (RCC) and to examine its significance in relation to tumor immune infiltration.

Materials And Methods: The correlation between FCRLA and data clinically related to RCC was explored using The Cancer Genome Atlas (TCGA), then validated using Gene Expression Omnibus (GEO) gene chip data. Enrichment and protein-protein interaction (PPI) network analyses were performed for FCRLA and its co-expressed genes.

Negative expression of CD117 predicted inferior OS and PFS in acute promyelocytic leukemia.

Introduction: In recent years, the correlation between CD117 antigen and the prognosis of hematological malignancies has been demonstrated. However, there is limited literature on the clinical significance of CD117 antigen in acute promyelocytic leukemia (APL). The aim of this study was to retrospectively analyze the clinical features and prognostic significance of CD117 in APL.

Recent advances in functional nucleic acid decorated nanomaterials for cancer imaging and therapy.

Nanomaterials possess unusual physicochemical properties including unique optical, magnetic, electronic properties, and large surface-to-volume ratio. However, nanomaterials face some challenges when they were applied in the field of biomedicine. For example, some nanomaterials suffer from the limitations such as poor selectivity and biocompatibility, low stability, and solubility.

Additional cytogenetic abnormalities in patients with newly diagnosed acute promyelocytic leukemia predict inferior event-free survival.

Background: The innovative combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has established a new chapter of curative approach in acute promyelocytic leukemia (APL). The disease characteristics and prognostic influence of additional cytogenetic abnormalities (ACA) in APL with modern therapeutic strategy need to be elucidated.

Methods: In the present study, we retrospectively investigated disease features and prognostic power of ACA in 171 APL patients treated with ATRA-ATO-containing regimens.

Enzymatic reaction modulated DNA assembly on graphitic carbon nitride nanosheets for sensitive fluorescence detection of acetylcholinesterase activity and inhibition.

A novel fluorescent strategy has been developed by using an enzymatic reaction modulated DNA assembly on graphitic carbon nitride nanosheets (CNNS) for the detection of acetylcholinesterase (AChE) activity and its inhibitors. The two-dimensional and ultrathin-layer CNNS-material was successfully synthesized through a chemical oxidation and ultrasound exfoliation method. Because of its excellent adsorption selectivity to ssDNA over dsDNA and superior quenching ability toward the fluorophore labels, CNNS were employed to construct a sensitive fluorescence sensing platform for the detection of AChE activity and inhibition.

Boronate carbon nanoparticles featuring efficient FRET for activatable two-photon fluorescence imaging of sialic acid surface-abundant tumor cells.

Two-photon carbon-based nanoprobes hold great potential for biomedical applications as a result of their advantages of low fluorescence background, deep tissue imaging penetration and enhanced spatial resolution. However, the development of an activatable two-photon fluorescence carbon-based nanoprobe that simultaneously has the ability to target desired organs or cells is highly desired but remained a largely unsolved challenge. Herein, we developed boronate affinity BCNP@MnO nanocomposites, constructed by one step growth of MnO nanosheets on the surface of aminophenylboronic acid-functionalized CNPs (BCNPs) a redox reaction, which can feature efficient fluorescence energy transfer quenching to the BCNPs, allowing for tumor-specific affinity recognition and two-photon fluorescence activation imaging.

A bipedal DNA nanowalker fueled by catalytic assembly for imaging of base-excision repairing in living cells.

DNA nanowalkers moving progressively along a prescribed DNA track are useful tools in biosensing, molecular theranostics and biosynthesis. However, stochastic DNA nanowalkers that can perform in living cells have been largely unexplored. We report the development of a novel stochastic bipedal DNA walker that, for the first time, realizes direct intracellular base excision repair (BER) fluorescence activation imaging.

DNAzyme cascade circuits in highly integrated DNA nanomachines for sensitive microRNAs imaging in living cells.

DNA molecular probes have emerged as powerful tools for fluorescence imaging of microRNAs (miRNAs) in living cells and thus elucidating functions and dynamics of miRNAs. In particular, the highly integrated DNA probes that can be able to address the robustness, sensitivity and consistency issues in a single assay system were highly desired but remained largely unsolved challenge. Herein, we reported for the first time that the development of the novel DNA nanomachines that split-DNAzyme motif was highly integrated in a single DNA triangular prism (DTP) reactor and can undergo target-activated DNAzyme catalytic cascade circuits, allowing amplified sensing and imaging of tumor-related microRNA-21 (miR-21) in living cells.

Cascade Circuits on Self-Assembled DNA Polymers for Targeted RNA Imaging In Vivo.

DNA molecular probes have emerged as a powerful tool for RNA imaging. Hurdles in cell-specific delivery and other issues such as insufficient stability, limited sensitivity, or slow reaction kinetics, however, hinder the further application of DNA molecular probes in vivo. Herein, we report an aptamer-tethered DNA polymer for cell-specific transportation and amplified imaging of RNA in vivo via a DNA cascade reaction.

A tumour mRNA-triggered nanoassembly for enhanced fluorescence imaging-guided photodynamic therapy.

A multifunctional theranostic nanoplatform, which integrates diagnostic and therapeutic functions in a single nanosystem, holds great promise for guiding disease treatment and improving the corresponding therapy efficacy. We report the development of a novel g-C3N4 nanosheet-based theranostic nanoassembly for both enhanced imaging of cancer-relevant mRNA in living cells and imaging-guided on-demand photodynamic therapy (PDT) for tumors. The nanoassembly was constructed by using highly fluorescent and water-dispersible g-C3N4 nanosheets which act as nanocarriers, enabling efficient and self-tracking transfection of the DNA hairpin probes.

Homogeneous label-free protein binding assay using small-molecule-labeled DNA nanomachine with DNAzyme-Based chemiluminescence detection.

Detecting the interactions between small molecules and proteins was critical for disease theranostics and drug development. Here we propose a novel universal assay strategy for monitoring small molecule-protein interactions in solution using strand displacement amplification (SDA) mediated by protein binding to small molecule with DNAzyme-based chemiluminescence detection. The DNA polymerase and nicking enzyme assisted SDA could yield a great amount of peroxidase-mimicking DNAzyme sequences which cause significantly chemiluminescence signals, while protein binding to the small molecule label would prevent DNA polymerase from extending nick site and DNAzyme sequence, and thus the chemiluminescence signals would obviously decrease.

DNAzyme activated protein-scaffolded CRISPR-Cas9 nanoassembly for genome editing.

A novel self-assembled protein-scaffolded CRISPR-Cas9 nanosystem for facile and efficient gene editing in a DNAzyme-controlled manner has been developed.

Proximity-induced hybridization chain assembly with small-molecule linked DNA for single-step amplified detection of antibodies.

A novel and versatile platform for single-step amplified fluorescence detection of antibodies via specific proximity-induced hybridization chain assembly is developed.

Programmable Self-Assembly of Protein-Scaffolded DNA Nanohydrogels for Tumor-Targeted Imaging and Therapy.

DNA hydrogels are biocompatible and are suitable for many biomedical applications. However, to be useful imaging probes or drug carriers, the ordinary bulk size of DNA hydrogels must be overcome. Here we put forward a new strategy for fabricating a novel and simple protein-scaffolded DNA nanohydrogel, constructed through a direct DNA self-assembly using three types of streptavidin (SA)-based DNA tetrad for the activation of imaging and targeting therapy of cancer cells.

Amplified Split Aptamer Sensor Delivered Using Block Copolymer Nanoparticles for Small Molecule Imaging in Living Cells.

We develop a novel amplified split aptamer sensor for highly sensitive detection and imaging of small molecules in living cells by using cationic block copolymer nanoparticles (BCNs) with entrapped fluorescent conjugated polymer as a delivery agent. The design of a split aptamer as the initiator of hybridization chain reaction (HCR) affords the possibility of enhancing the signal-to-background ratio and thus allows high-contrast imaging for small molecules with relatively weak interactions with their aptamers. The novel design of using fluorescent cationic BCNs as the nanocarrier enables efficient and self-tracking transfection of DNA probes.

Multivalent Self-Assembled DNA Polymer for Tumor-Targeted Delivery and Live Cell Imaging of Telomerase Activity.

The efficient detection and in situ monitoring of telomerase activity is of great importance for cancer diagnosis and biomedical research. Here we report for the first time that the development of a novel multivalent self-assembled DNA polymer, constructed through telomerase primer sequence (I) triggered hybridization chain assembly using two functional hairpin probes (tumor-trageting aptamer modified H1 and signal probe modified H2), for sensitive detection and imaging of telomerase activity in living cells. After internalizing into the tumor cells by multivalent aptamer targeting, the I on DNA polymers can be elongated by intracellular telomerase to generate telomere repeat sequences that are complementary with the signal probe, which can proceed along the DNA polymers, and gradually light up the whole DNA polymers, leading to an enhanced fluorescence signal directly correlated with the activity of telomerase.

DNA Polymer Nanoparticles Programmed via Supersandwich Hybridization for Imaging and Therapy of Cancer Cells.

Spherical nucleic acid (SNA) constructs are promising new single entity materials, which possess significant advantages in biological applications. Current SNA-based drug delivery system typically employed single-layered ss- or ds-DNA as the drug carriers, resulting in limited drug payload capacity and disease treatment. To advance corresponding applications, we developed a novel DNA-programmed polymeric SNA, a long concatamer DNA polymer that is uniformly distributed on gold nanoparticles (AuNPs), by self-assembling from two short alternating DNA building blocks upon initiation of immobilized capture probes on AuNPs, through a supersandwich hybridization reaction.

Cell Surface-Anchored DNA Nanomachine for Dynamically Tunable Sensing and Imaging of Extracellular pH.

DNA nanodevices that mimic natural biomolecular machines changing configurations in response to external inputs have enabled smart sensors to live cell imaging. We report for the first time the development of a dynamic DNA nanomachine that is anchored on a cell's surface and undergoes pH-responsive triplex-duplex conformation switching, allowing tunable sensing and imaging of extracellular pH. Results reveal that the DNA nanomachine can be stably anchored on the cell surface via multiple anchors, and the adjustment of CG-C content in the switch element confers tunability of pH response windows.

A multiplex paper-based nanobiocatalytic system for simultaneous determination of glucose and uric acid in whole blood.

In this work, a versatile point-of-care assay platform based on a microfluidic paper-based analytic device (μPAD) was developed for the simultaneous detection of multiple targets. The μPAD with a central zone and six test zones is fabricated by a simple and inexpensive wax printing method. A flower-like hybrid nanocomplex synthesized with specific dual enzymes and Cu3(PO4)2 inorganic nanocrystals is spotted in the test zones on the μPAD, followed by the introduction of assay targets.

Tumor-selective catalytic nanosystem for activatable theranostics.

A novel tumor-selective catalytic nanosystem that enables efficient chemodynamic therapy (CDT) and activatable fluorescence imaging in H2O2-rich tumor microenvironments has been developed.

Tumor-Targeted Graphitic Carbon Nitride Nanoassembly for Activatable Two-Photon Fluorescence Imaging.

Unique physicochemical characteristics of graphitic carbon nitride (g-CN) nanosheets suit them to be a useful tool for two-photon fluorescence bioimaging. Current g-CN nanosheets based imaging probes typically use the "always-on" design strategies, which may suffer from increased fluorescence background and limited contrast. To advance corresponding applications, g-CN nanosheets based activatable two-photon fluorescence probes remain to be explored.

Branched Hybridization Chain Reaction Circuit for Ultrasensitive Localizable Imaging of mRNA in Living Cells.

Hybridization chain reaction (HCR) circuits are valuable approaches to monitor low-abundance mRNA, and current HCR is still subjected to issues such as limited amplification efficiency, compromised localization resolution, or complicated designs. We report a novel branched HCR (bHCR) circuit for efficient signal-amplified imaging of mRNA in living cells. The bHCR can be realized using a simplified design by hierarchically coupling two HCR circuits with two split initiator fragments of the secondary HCR circuit incorporated in the probes for the primary HCR circuit.