The goal of this research is to develop mesostructured hybrid silica-based nanoparticles functionalized with aptamers for targeted delivery of therapeutic RNA-based nanostructures and small molecules for cancer treatment.
Kirill Afonin (CHEM), and Juan Vivero-Escoto (CHEM)
Cancer is one of the most deadly diseases of our time. Over the past few years, the number of siRNA-based clinical trials to treat cancer disease has increased significantly. The use of RNA nanoparticles (RNA NPs) functionalized with multiple siRNAs provides precise control over the formulation to achieve higher local concentration of therapeutic siRNAs. However, there are several concerns such as rapid degradation of RNA in human blood and ineffective crossing of biological membranes due to RNA’s negative charge that preclude the broad pharmacological application of RNA therapeutics. These problems are normally addressed by using synthetic carriers. Mesoporous silica nanoparticles (MSNs) can be used to effectively deliver functional RNA nanoparticles. Additionally, the resulting materials can be decorated with aptamers specifically designed to bind to cancer cells. These multifunctional MSN-based platforms have the potential to completely change the way we treat cancer by increasing the numbers of the simultaneously-delivered multiple drugs while minimizing their toxicity.
In this project, we will synthesize siRNA NPs with improved therapeutic properties (Dr. Afonin). The siRNA NPs will be incorporated to MSNs, which are functionalized with anticancer drugs such as cisplatin and docetaxel (Dr. Vivero-Escoto). The nanoconstruct will be further modified with aptamers as targeting agents. The therapeutic properties of the siRNA-MSN platform will be tested in vitro using a wide variety of cancer cells lines (Dr. Afonin and Dr. Vivero-Escoto).
REU Students’ Role
The student(s) in Dr. Afonin’s lab will learn how to fabricate RNA-base nanoparticles functionalized with different siRNAs and fluorophores. Students are expected to participate in all steps leading to the production and detailed analysis of RNA nanoparticles in vitro. Several basic techniques such as PCR, in vitro transcription, RNA purification, RNA assemblies, various gel electrophoresis, etc, will be learned by the students during this project.
The student(s) in Dr. Vivero-Escoto’s lab will be involved with the synthesis and characterization of MSNs. These materials will be characterized by a wide variety of techniques such as dynamic light scattering, thermogravimetric analysis, surface analyzer, and scanning and transmission electron microscopy. The student(s) will also participate in the functionalization and characterization of the MSN materials with anticancer drugs, siRNA NPs and aptamers. In addition, the student(s) will carry out in vitro experiments to determine the therapeutic effect of the siRNA-MSN platform against cancer cell lines.