P.E. Vivas-Mejia, N. Grafals
University of Puerto Rico Medical Sciences Campus,
United States
Keywords: AuNP, liposomas, miRNA, RNAi, brain, GBM
Summary:
Glioblastoma (GBM) is the most malignant form of all primary brain tumors, and it is responsible for around 200,000 deaths each year worldwide. The standard therapy for GBM treatment includes surgical resection followed by temozolomide-based chemotherapy and/or radiotherapy. With this treatment, the median survival rate of GBM patients is 12-15 months after its initial diagnosis. Therefore, novel and better treatment modalities for GBM patients are urgently needed. MicroRNAs (miRNAs) are endogenous small non-coding RNAs that regulate gene expression at the post-transcriptional level. The initiation, progression, and infiltration ability of GBMs are attributed in part to the dysregulation of microRNAs (miRNAs). Targeting upregulated miRNAs with oligonucleotide miRNA inhibitors (OMIs) is a promising strategy for GBM treatment. Therapies with RNA oligonucleotides are commonly named as interference RNA (RNAi). Despite positive outcomes in the laboratory, the clinical translation of RNAi is developing slowly due to hurdles like fast renal clearance, low incorporation into cancer cells and activation of immune responses. Part of these obstacles has been solved using nanoparticles (NPs) for systemic delivery of RNAi-related molecules. NPs for GBM treatment encounter an additional challenge as they need to cross the blood brain barrier (BBB), the anatomical barrier that protects the brain from foreign substances. In fact, 98% of drugs with therapeutic potential fails to cross the BBB. Therefore, creating NPs that enable efficient delivery of RNAi-based therapies through the BBB and into GBM tumors is of high clinical relevance. We developed a gold-liposome NP (Au-L-NP) formulation that crossed the BBB and was significantly accumulated in the tumor cells of a syngeneic GBM mouse model. This formulation can be used to the treatment of brain-related conditions.