RNA Nanoparticle for Treatment of Gastric Cancer

The presently-disclosed subject matter relates to RNA-based composition and method to treat gastric cancer in a subject. More particularly, the presently disclosed subject matter relates to a RNA nanostructure and composition containing a multiple branched RNA nanoparticle, a gastric cancer targeting module, and an effective amount of a therapeutic agent. Further, the presently disclosed subject matter relates to a method of using the RNA nanoparticle composition to treat gastric cancer in a subject having or at risk of having gastric cancer

Regression of Gastric Cancer by Systemic Injection of RNA Nanoparticles Carrying Both Ligand and siRNA

Gastric cancer is the second leading cause of cancer-related death worldwide. RNA nanotechnology has recently emerged as an important field due to recent finding of its high thermodynamic stability, favorable and distinctive in vivo attributes. Here we reported the use of the thermostable three-way junction (3WJ) of bacteriophage phi29 motor pRNA to escort folic acid, a fluorescent image marker and BRCAA1 siRNA for targeting, imaging, delivery, gene silencing and regression of gastric cancer in animal models. In vitro assay revealed that the RNA nanoparticles specifically bind to gastric cancer cells, and knock-down the BRCAA1 gene. Apoptosis of gastric cancer cells was observed. Animal trials confirmed that these RNA nanoparticles could be used to image gastric cancer in vivo, while showing little accumulation in crucial organs and tissues. The volume of gastric tumors noticeably decreased during the course of treatment. No damage to important organs by RNA nanoparticles was detectible. All the results indicated that this novel RNA nanotechnology can overcome conventional cancer therapeutic limitations and opens new opportunities for specific delivery of therapeutics to stomach cancer without damaging normal cells and tissues, reduce the toxicity and side effect, improve the therapeutic effect, and exhibit great potential in clinical tumor therapy

Nanoparticle Orientation to Control RNA Loading and Ligand Display on Extracellular Vesicles for Cancer Regression

Nanotechnology offers many benefits, and here we report an advantage of applying RNA nanotechnology for directional control. The orientation of arrow-shaped RNA was altered to control ligand display on extracellular vesicle membranes for specific cell targeting, or to regulate intracellular trafficking of small interfering RNA (siRNA) or microRNA (miRNA). Placing membrane-anchoring cholesterol at the tail of the arrow results in display of RNA aptamer or folate on the outer surface of the extracellular vesicle. In contrast, placing the cholesterol at the arrowhead results in partial loading of RNA nanoparticles into the extracellular vesicles. Taking advantage of the RNA ligand for specific targeting and extracellular vesicles for efficient membrane fusion, the resulting ligand-displaying extracellular vesicles were capable of specific delivery of siRNA to cells, and efficiently blocked tumour growth in three cancer models. Extracellular vesicles displaying an aptamer that binds to prostate-specific membrane antigen, and loaded with survivin siRNA, inhibited prostate cancer xenograft. The same extracellular vesicle instead displaying epidermal growth-factor receptor aptamer inhibited orthotopic breast cancer models. Likewise, survivin siRNA-loaded and folate-displaying extracellular vesicles inhibited patient-derived colorectal cancer xenograft

Impact of water on miscibility characteristics of the CO2/n-hexadecane system using the pendant drop shape analysis method

Miscible CO2 flooding has shown bright prospects for improving oil recovery from unconventional reservoirs as well as for storing greenhouse gas in underground formations. Although the favorable water presence effect has been reported in the near miscible CO2 flooding practices, there is still a lack of target research works on the impact of water on the miscibility characteristics of the oil/gas systems. Therefore in this paper, the effect of water presence on the Minimum Miscibility Pressure (MMP) of the CO2/n-Hexadecane (n-C16H34) system is experimentally investigated based on the Oil Droplet Volume Measurement (ODVM) method. By pre-saturating CO2 with water in the high-pressure high-temperature cell, the water component is introduced at the CO2/oil interface. Measurement results show the water presence could result in lower MMPs of the CO2/oil system. Under five temperature levels of 40 °C, 51 °C, 61 °C, 72 °C, and 82 °C, the water presence decreases the MMPs of the CO2/n-C16H34 system from 8.2 to 7.8 MPa, from 9.6 to 8.8 MPa, from 11.6 to 10.2 MPa, from 13.0 MPa to 12.2 MPa and from 14.6 MPa to 13.2 MPa respectively. Thermodynamic calculations provide consistent results as the experimental observations, indicating the main mechanism behind the lower MMPs of the water presence CO2/oil system could be the decreased CO2 molar fraction in the water presence system. This research is expected to provide an innovative viewpoint to understand the water presence effect in the CO2 flooding processes

MicroRNA-378-3p/5p suppresses the migration and invasiveness of oral squamous carcinoma cells by inhibiting KLK4 expression

Distant metastasis frequently occurs in oral squamous cell carcinoma (OSCC) and contributes to the adverse prognosis of OSCC. However, the potential mechanisms have not been clarified yet. This study aimed to evaluate the role of miR-378 in the migration and invasion of OSCC in vitro and in vivo. According to our results, the migration and invasion abilities were increased in miR-378-overexpressing cells, while decreased in miR-378-3p/5p-silencing cells. In addition, overexpression of miR-378 suppressed the expressions and activities of MMP-9 and MMP-2. Epithelial-mesenchymal transition (EMT) was restrained by overexpression of miR-378 as evidenced by increase in E-cadherin expression and decrease in N-cadherin and uPA expression. However, the miR-378-3p/5p knockdown groups had the opposite results. Moreover, kallikrein-related peptidase 4 (KLK4) was confirmed to be a target gene of miR-378. Overexpression of KLK4 reversed miR-378 overexpression-induced decrease in migration and invasion via upregulating MMP-9, MMP-2, and N-cadherin levels, while downregulating E-cadhrin level. Finally, the number of metastasis nodules in the lung tissues of nude mice was reduced by overexpression of miR-378, whereas the metastasis nodule number was raised by miR-378 knockdown. Taken together, our study suggests that miR-378/KLK4 axis is involved in the mechanisms of the migration and invasion of OSCC cells. Targeting miR-378/KLK4 axis may be an effective measure for treating OSCC.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author