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

Abstract

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.

EGFR Antibody Conjugated Bimetallic Au@Ag Nanorods for Enhanced SERS-Based Tumor Boundary Identification, Targeted Photoacoustic Imaging and Photothermal Therapy

“…In our previous work, with the aim of finding early gastric cancer, we screen out some new biomarkers associated with early gastric cancer and develop novel ultrasensitive detection methods [8][9]. We also designed and fabricated some multifunctional nanoprobes for targeted imaging and simultaneous therapy of subcutaneous and in situ gastric cancer tissues with 5 mm in diameter [10][11][12][13][14][15][16][17][18][19][20][21][22]. Among those multifunctional nanoprobes, RGDconjugated gold nanorods could target tumor tissues and kill tumor cells via photothermal therapy [14], exhibiting potential clinical application prospects.…”

High-purified Isolation and Proteomic Analysis of Urinary Exosomes from Healthy Persons

“…MiRNA-221 in exosomes from bone marrow mesenchymal stem cells could activate oncogenic activity in gastric cancer [22]. Although gastric cancer biomarkers and theranostics have made great advance [23,24,25,26]; some miRNAs have also been found to be associated with gastric cancer stages [27], how the exosomal proteins involved in the progression of cancer still lacks report. Li, et al reported that exosomal proteins were used for cancer diagnosis, were potential biomarkers [28], and could also be used for cardiac angiogenesis [29], tumor therapy [30] and (hepatitis B virus) HBV therapy [31].…”

Advance and Prospects of Nanotheranostic Technology for Gastric Cancer

“…To characterize the structure of the RNA constructs, the 3WJ nanoparticles were extended by 39-60 base-pairs (in red color), which is within the persistence length of dsRNA and will not affect the 3WJ folding as described before, to generate the AFM image as shown. Reprinted with permission from Nature Press [43]. nanoprobes in MGC-803 tumor-bearing nude mice reveal their superior penetration and retention behavior in tumors, while the preserved features of renal clearance and stealthy to reticuloendothelial system are mainly attributed to the small hydrodynamic diameters and the FA-capped PEGylated ligands.…”

“…Our objective is to construct multi-functional, thermodynamically and chemically stable RNA nanoparticles harboring sequences that allow specific binding to stomach cancer specific cell surface antigens or receptors resulting in the internalization of RNA nanoparticles into target cells and delivery of the siRNA, miRNA, and drugs for attaining synergistic effects for the treatment of stomach cancer, we also investigated the effects of prepared RNA nanoparticles on the regression of gastric cancer tissues in vivo, and potential molecular mechanism, with the aim of laying foundation for further clinical application in near future [42,43].…”