LAUSR

Glioblastoma Multiforme (GBM) is the deadliest type of primary brain tumor being responsible for more than 14,000 deaths annually. The survival rate of GBM patients from time of diagnosis is 5 months if left untreated and 15 months with standard care of treatment. Despite great research efforts in the last 30 years, GBM survival rate has only increased by 2%. This is mostly due to high recurrence, treatment resistance, and the existence of the blood brain barrier (BBB) which restricts drug delivery to the tumor tissue. Therefore, the development of novel therapeutic modalities able to cross the BBB is urgently needed. MicroRNAs (miRNAs) are small (18-22 nt.) non-coding RNAs that regulate gene expression at the post-transcriptional level by binding to the 3’UTR of target mRNAs. Several dysregulated miRNAs have been reported in all tumor types, including GBM. Targeting oncogenic miRNAs with oligonucleotide miRNA inhibitors (OMIs) in vitro has shown therapeutic potential. However, in vivo administration requires the development of nanocariers capable of increasing the stability of OMIs in circulation and improving their delivery to target tissues. In addition, nanocarriers that can overcome the BBB are needed. The most studied and promising nanocarriers are gold nanoparticles (AuNP) and liposomes. While AuNPs have bioimaging and microscopy advantages, liposomes are clinically preferred. Therefore, we propose encapsulating OMIs-AuNPs to BBB targeted liposomes. In this study we present the characterization of miRNA inhibitors conjugated to AuNP. Briefly, 15 nm AuNP were functionalized to OMIs by two different techniques: Salt aging functionalization method and PEG and surfactant assisted conjugation method. Afterwards, both nanoconjugates were analyzed for particle size, zeta potential and loading capacity. The PEG and surfactant assisted functionalization proved to be superior in all of the analysis, resulting in 30 nm OMIs-AuNPs with a zeta potential of -8 mV and a loading capacity ratio of 64 oligonucleotides per AuNP. Further characterization studies such as cell internalization and cytotoxicity are under evaluation. Citation Format: Nilmary Grafals, Blanca I. Quinones, Pablo E. Vivas, Gabriel Barletta. Targeting microRNAs in brain tumors with oligonucleotide nanoparticle conjugates [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3105. doi:10.1158/1538-7445.AM2017-3105