Molecular Spherical Nucleic Acids for Glioblastoma Treatment

Objective

The complexity of cancer arises from its ability to manifest in numerous ways. Therefore, it is one of the most significant health challenges today, with the WHO reporting 20 million new cases and 9.7 million deaths in 2022. Traditional treatments, such as surgery and chemotherapy, have important collateral damages causing severe side effects because of their lack of specificity. Gene therapy, particularly RNA interference (RNAi) using small interfering RNA (siRNA), has emerged as a targeted approach that consists of silencing oncogene expression, causing the subsequent inhibition of the production of harmful proteins. However, delivering siRNA to cells remains a challenge due to its poor cell membrane transfection and rapid degradation. To overcome these issues, spherical nucleic acids (SNAs), defined as nanoscale constructs in which nucleic acids are densely packed and highly oriented on the surface of spherical core, were postulated as effective carriers. Unfortunately, current nanosized cores face and optimization hurdles due to, lack of structural definition, complexity on synthetic procedures and toxicity. In response, I propose the development of molecular SNAs. The novelty of this proposal entails the use of Metal-Organic Polyhedra (MOPs) as molecularly defined hollow core for SNAs. Particularly, the project siRNA-MOPs aims to combine gene delivery and drug encapsulation in a single delivery system and, ultimately, apply this gene chemotherapy approach to glioblastoma treatment.