A Comparative Study on the DNA Interactions and Biological Activities of Benzophenanthridine and Protoberberine Alkaloids.

Numerous small molecules exert antitumor effects by interacting with DNA, thereby influencing processes, such as DNA replication, transcription, meiosis, and gene recombination. Benzophenanthridine and protoberberine alkaloids are known to bind DNA and exhibit many pharmacological activities. In this study, we conducted a comparative analysis of the interactions between these two classes of alkaloids with G-quadruplex (G4) DNA and double-stranded DNA (dsDNA).

A Bispecific Chimeric Aptamer Design Platform Based on c-MET Aptamer with a Replaceable Redundant Region.

Molecular engineering enables the creation of aptamers with novel functions, but the prerequisite is a deep understanding of their structure and recognition mechanism. The cellular-mesenchymal epithelial transition factor (c-MET) is garnering significant attention due to the critical role of the c-MET/HGF signaling pathway in tumor development and invasion. This study reports a strategy for constructing novel chimeric aptamers that bind to both c-MET and other specific proteins.

Heptamethine Cyanine-Based Molecule Release Triggered by Mitochondrial ROS.

Conditionally activated molecule release in live cells would provide spatiotemporal control for the study and intervention of biological processes, e.g., bioactive molecule monitoring and controlled drug release.

DNA Aptamer Binding Octapeptide Repeat Region of Cellular Prion Protein.

Cellular prion protein (PrP) is highly expressed in a variety of tumor cells and plays a crucial role in neurodegenerative diseases. Its N-terminal domain contains a conserved octapeptide (PHGGGWGQ) repeat sequence. The number of repeats has been correlated with the species as well as the development of associated diseases.

Structural Optimization and Interaction Study of a DNA Aptamer to L1 Cell Adhesion Molecule.

The L1 cell adhesion molecule (L1CAM) plays important roles in the development and plasticity of the nervous system as well as in tumor formation, progression, and metastasis. New ligands are necessary tools for biomedical research and the detection of L1CAM. Here, DNA aptamer yly12 against L1CAM was optimized to have much stronger binding affinity (10-24 fold) at room temperature and 37 °C via sequence mutation and extension.

A mitochondria-targeted fluorescent probe for imaging of endogenous carbon monoxide in living cells.

Carbon monoxide (CO), a vital gasotransmitter, plays critical functions in many physiological processes. Mitochondrial CO is closely related to mitochondrial respiration, thus the detection and imaging of mitochondrial CO in living cells is very important and has attracted much attention recently. In this paper, we developed a hemicyanine-based off-on fluorescent probe, CO-H1, which was used for monitoring endogenous mitochondrial CO levels in living cells.

Generation of an Aptamer Targeting Receptor-Type Tyrosine-Protein Phosphatase F.

Cell-SELEX is a powerful tool to generate aptamers that specifically bind the native molecules on living cells. Here, we report an aptamer ZAJ4a generated by cell-SELEX. The molecular target of ZAJ4a was pulled down by the enriched cell-SELEX pool and identified to be the receptor-type tyrosine-protein phosphatase F (PTPRF) through a stable isotope labeling using amino acids in cell culture (SILAC)-based quantitative proteomic method.

A photo-activated aptamer-drug conjugate for targeted drug delivery.

A photo-activated aptamer-drug conjugate, HG1-9-DNP, was developed based on an aptamer HG1-9 and a photolabile naphthalimide derivative DNP. HG1-9-DNP could be internalized into cells mediated by TfR, then photocleaved, and released a promising cytotoxic agent, DNNH, which arrested the cell cycle at the G2/M phase, resulting in high photo-induced cytotoxicity.

Potential G-quadruplexes within the Promoter Nuclease Hypersensitive Sites of the Heat-Responsive Genes in Rice.

G-quadruplexes (G4s) have been shown to be involved in the regulation of multiple cellular processes. Exploring putative G4-forming sequences (PQSs) in heat-responsive genes of rice and their folding structures under different conditions will help to understand the mechanism in response to heat stress. In this work, we discovered a prevalence of PQSs in nuclease hypersensitive sites within the promoters of heat-responsive genes.

Characterization and Identification of Aptamers against CD49c for the Detection, Capture, and Release of Cancer Cells.

As a kind of recognition molecule, aptamers can be inserted into some regulatory sequences for the smart response of their targets. However, the molecular engineering might lead to the change of the binding affinity. Here, we present a stable aptamer ZAJ-2c and an environmentally sensitive aptamer ZAJ-2d optimized from an original cell-binding aptamer ZAJ-2, and the molecular target was further identified as CD49c on the cell membrane.

A mitochondria-targeted near-infrared fluorescent probe for detection and imaging of HSO in living cells.

Sulfur dioxide, an essential gas signaling molecule mainly produced in mitochondria, plays important roles in many physiological and pathological processes. Herein, a near-infrared fluorescent probe, A1, with good mitochondria targeting ability was developed for colorimetric and fluorescence detection of HSO. Probe A1 has a conjugated cyanine structure that can selectively react with HSO through the nucleophilic addition.

Aptamer-Based Cell Nucleus Imaging via Expansion Microscopy.

Expansion microscopy (ExM) is a newly developed technology in recent years that enables nanoscale imaging under conventional microscopes. Herein, we report an aptamer-based ExM imaging strategy. A nucleus-targeting aptamer Ch4-1 was chemically labeled with a dye and an acrydite at each end to perform the functions of molecular recognition, fluorescence reporting, and gel anchoring.

Transferrin receptor-mediated internalization and intracellular fate of conjugates of a DNA aptamer.

Aptamers have excellent specificity and affinity in targeting cell surface receptors, showing great potential in targeted delivery of drugs, siRNA, mRNA, and various nanomaterials with therapeutic function. A better insight of the receptor-mediated internalization process of aptameric conjugates could facilitate the design of new targeted drugs. In this paper, human transferrin receptor-targeted DNA aptamer (termed HG1-9)-fluorophore conjugates were synthesized to visualize the internalization, intracellular transport, and nano-environmental pH of aptameric conjugates.

Cell-SELEX-based selection of ssDNA aptamers for specifically targeting V600E-mutated melanoma.

Malignant melanoma is regarded as the most aggressive form of skin cancer, and is responsible for most death caused by skin cancer. mutations occur in approximately 40-50% of melanomas, with V600E being the most common mutation. Testing for mutations and targeted therapy have markedly improved long-term survival for patients with -mutated melanoma.

p-Aminostyryl thiazole orange derivatives for monitoring mitochondrial viscosity in live cells.

Viscosity of cell microenvironment plays a significant role in maintaining the normal life activities of cells. Particularly, the abnormal viscosity in mitochondria is closely associated with lots of diseases and cellular dysfunctions. Herein, we developed a group of p-aminostyryl thiazole orange derivatives with different amino side chains.

A DNA Aptameric Ligand of Human Transferrin Receptor Generated by Cell-SELEX.

General cancer-targeted ligands that can deliver drugs to cells have been given considerable attention. In this paper, a high-affinity DNA aptamer (HG1) generally binding to human tumor cells was evolved by cell-SELEX, and was further optimized to have 35 deoxynucleotides (HG1-9). Aptamer HG1-9 could be taken up by live cells, and its target protein on a cell was identified to be human transferrin receptor (TfR).

A 4-aminonaphthalimide-based fluorescent traceable prodrug with excellent photoinduced cytotoxicity.

A blue light activated anti-cancer prodrug, NST, was designed based on a photoactive 4-aminonaphthalimide derivative and an anticancer drug, 10-hydroxycamptothecin. NST was hard to be taken up by living cells and showed negligible dark cytotoxicity. The irradiation caused photocleavage of NST and resulted in high cytotoxicity.

Ratiometric detection and imaging of hydrogen sulfide in mitochondria based on a cyanine/naphthalimide hybrid fluorescent probe.

Hydrogen sulfide (H2S) in mitochondria plays important roles in many mitochondria-related physiological and pathological processes. Herein, a cyanine/naphthalimide hybrid fluorescent probe, L1, was designed for the ratiometric detection and imaging of mitochondrial H2S, in which cyanine and naphthalimide were used as the mitochondria-targeting group and H2S response group, respectively. Besides its good mitochondria-targeting ability, L1 also showed high sensitivity and good selectivity for H2S.

FnCas12a/crRNA assisted dumbbell-PCR detection of IsomiRs with terminal and inner sequence variants.

Herein, we report a FnCas12a/crRNA assisted Dumbbell-PCR method for the detection of isomiRs with double specificity and magnification. The single nucleotide variant of isomiRs in terminals and/or inner sequence could be discriminated by this strategy. Using this method, let-7a isomiRs in MCF-7 and MCF-7R cell lines were analyzed.

Cell-SELEX, an Effective Way to the Discovery of Biomarkers and Unexpected Molecular Events.

Cell-SELEX can not only generate aptamers for specific cell isolation/detection, diagnosis, and therapy, but also lead to the discovery of biomarkers and unexpected molecular events. However, most cell-SELEX research is concentrated on aptamer generation and applications. In this progress report, recent research progress with cell-SELEX in terms of the discovery of biomarkers and unexpected molecular events is highlighted.

Prion Protein Targeted by a Prostate Cancer Cell Binding Aptamer, a Potential Tumor Marker?

Cell-SELEX is an effective strategy to discover aptamers that can distinguish the molecular signatures of target cells from control cells. The molecular targets of such aptamers have the potential to be biomarkers. Here, we report target identification of aptamer wy-5a generated by cell-SELEX against a prostate cancer cell line, PC-3.

Thiazole Orange Styryl Derivatives as Fluorescent Probes for G-Quadruplex DNA.

G-quadruplex (G4) forming sequences commonly exist in the genome and are closely related to gene regulation and expression. Development of a fluorescent probe that can specifically recognize G4 is essential for studying its structures and biological functions. Thiazole orange (TO) is an often used nucleic acid dye that is reported to have higher affinity to G4 DNA than double-stranded (ds) DNA.

Immunomodulatory Effects of Polysaccharide Extract and Its Uptake Behaviors at the Cellular Level.

L. is a widely used functional food and medicinal herb in Asian countries. polysaccharides (LBP) are considered as one of the major medicinal components of fruit and exhibits a wide range of biological activities.

Detection of Circulating Tumor-Related Materials by Aptamer Capturing and Endogenous Enzyme-Signal Amplification.

Circulating tumor-related materials (CTRMs) shed from original or metastatic tumors, carry a lot of tumor information and are considered as important markers for cancer diagnosis and metastasis prognosis. Herein, we report a colorimetric detection strategy for CTRMs based on aptamer-based magnetic isolation and endogenous alkaline phosphatase (AP)-signal amplification. This strategy exhibited high sensitivity and selectivity toward the CTRMs that express AP heterodimers (the target of aptamer, a potential tumor marker).