Computable structured aptamer for targeted treatment of ovarian cancer.

Nucleolin protein expression is higher on the ovarian cancer cell surface. AS1411, a DNA aptamer, can bind with nucleolin protein specifically. In this study, we developed HA and ST DNA tiles to assemble six AS1411 aptamers to deliver doxorubicin. In addition, to superior serum stability and drug loading, HA-6AS and ST-6AS outperformed TDN-AS in cellular uptake. HA-6AS and ST-6AS exhibited satisfactory targeted cytotoxicity and achieved resounding lysosomal escape. Moreover, when injected into nude mice subcutaneous xenograft models, HA-6AS reached the peak in tumor more quickly than ST-6AS, and better expressed the active targeting ability of AS1411. Our study suggests that designing appropriate DNA tiles to assemble different aptamers to deliver different chemotherapeutic drugs is a promising treatment for ovarian cancer.

DNA origami frame filled with two types of single-stranded tiles.

DNA origami and DNA single-stranded tiles (SSTs) are two basic motifs that are widely used in fabricating DNA nanostructures. Typically, DNA origami is self-folded via a long single phage strand (scaffold strand) and this process is aided by a myriad of short oligonucleotides (staple strand). Unlike DNA origami, SSTs construct nanostructures using many unique strands connected with each other to obtain specific shapes. These motifs are material- and labour-consuming, and require multiple different synthetic oligonucleotides, and DNA SSTs tend to remain kinetically trapped in the form of tubes. In this study, we present a new strategy that combines DNA origami with DNA SSTs to construct a DNA nanostructure with a predesigned shape. A rectangular DNA origami frame with ten dozen helper strands was filled with two types of SSTs assembled repeatedly, which avoided the kinetic trap and used fewer synthetic oligonucleotides. The assembly results were identified using atomic force microscopy. The experimental analysis demonstrated the stability and feasibility of the strategy.

Detect the early-warning signals of diseases based on signaling pathway perturbations on a single sample.

BACKGROUND: During the pathogenesisof complex diseases, a sudden health deterioration will occur as results of the cumulative effect of various internal or external factors. The prediction of an early warning signal (pre-disease state) before such deterioration is very important in clinical practice, especially for a single sample. The single-sample landscape entropy (SLE) was proposed to tackle this issue. However, the PPI used in SLE was lack of definite biological meanings. Besides, the calculation of multiple correlations based on limited reference samples in SLE is time-consuming and suspect. RESULTS: Abnormal signals generally exert their effect through the static definite biological functions in signaling pathways across the development of diseases. Thus, it is a natural way to study the propagation of the early-warning signals based on the signaling pathways in the KEGG database. In this paper, we propose a signaling perturbation method named SSP, to study the early-warning signal in signaling pathways for single dynamic time-series data. Results in three real datasets including the influenza virus infection, lung adenocarcinoma, and acute lung injury show that the proposed SSP outperformed the SLE. Moreover, the early-warning signal can be detected by one important signaling pathway PI3K-Akt. CONCLUSIONS: These results all indicate that the static model in pathways could simplify the detection of the early-warning signals.

Applications of Aptamers in the Diagnosis and Treatment of Ovarian Cancer: Progress From 2016 to 2020.

Nucleic acid aptamers are short single-stranded DNA or RNA oligonucleotides selected from a random single-stranded nucleic acid library using systematic evolution of ligands by exponential enrichment technology. To allow them to bind to molecular targets with the same specificity and precision as that of antibodies, aptamers are folded into secondary or tertiary structures. However, compared to antibodies, aptamers are not immunogenic and are easier to synthesize. Furthermore, they are chemically modified, which protects them from degradation by nucleases. Hence, due to their stability and favorable targeting ability, aptamers are promising for the diagnosis and treatment of diseases. Ovarian cancer has the worst prognosis among all gynecological diseases and is usually diagnosed at the medium and advanced stages due to its nonspecific symptoms. Relapse is common, even if patients receive a standard therapeutic regimen including surgery and chemotherapy; simultaneously, drug resistance and adverse effects are reported in a several patients. Therefore, the safer and more efficient diagnostic and treatment method for ovarian cancer is imperative. Scientists have been trying to utilize aptamer technology for the early diagnosis and accurate treatment of ovarian cancer and some progress has been made in this field. This review discusses the screening of nucleic acid aptamers by targeting ovarian cancer cells and the application of aptamers in the diagnosis and treatment of ovarian cancer.