Abstract MicroRNAs are non-coding RNA molecules that regulate more than 60% of the protein coding genes and their dysregulation has proven to be involved in the initiation, progression and maintenance of malignant brain tumors such as glioblastoma multiforme (GBM). Targeting microRNAs in GBM has shown therapeutic value, although their translation to the clinic have been halted due to their rapid renal clearance, short circulatory life and inability to reach the brain tumor after systemic administration. Over the last years, nanodelivery systems such as liposomes (Lip) and gold nanoparticles (AuNPs) have gained acceptance for the treatment of cancer. This project is focused on developing anti-miRNA gold carriers further encapsulated inside nanoliposomes that are labeled with blood brain barrier specific peptides (Apolipoprotein E and Rabies Virus Glycoprotein). The synthesis of these dual gold-liposomal particles has three important steps: (a) Peptide Pegylation, (b) anti-microRNA conjugation to gold nanoparticles and, (c) nanoparticle assembly. To achieve each of them the corresponding peptide was conjugated to 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N[methoxy(polyethylene glycol)]-Malemide (DSPE-PEG-Mal) by a thioester bond and incorporated into DOPC and cholesterol lipid mixture. Afterwards, anti-microRNAs were functionalized to 15 nm gold nanoparticles (AuNPs) to obtain RNAi-AuNPs. Finally, the nanoparticles of interest where produce: RNAi-AuNP-Lip, RNAi-AuNP-Lip-APOE and RNAi-AuNP-Lip-RVG. These nanoparticles where characterized by dynamic light scattering, zeta potential and encapsulation efficiency. Additionally, we determine their toxicity in U-87 GBM cell lines. Our results obtained show sizes that range from 30 nm, 60 nm and 95 nm for gold-RNAi, gold-liposomes and gold-liposome-peptides respectively. These particles are slightly negative and have encapsulation efficiencies that are greater than 50%. Cell viability analysis also show that gold nanoparticles carrying microRNA inhibitor negative controls are not toxic to GBM cell lines. Additional studies for cell internalization, reactive oxygen species generation and RNA delivery and release are ongoing now. Developing systemic viable microRNA based therapeutics its a big challenge, but they are crucial to assure the patient a non-invasive therapy that could improve their quality of life and their overall survival. Citation Format: Nilmary Grafals, Blanca I. Quiñoes-Diaz, Janixa Del Valle, Gabriel L. Barletta-Bonano, Pablo E. Vivas-Mejía. Developing brain tumor-specific gold-liposomal nanocarriers for a noninvasive delivery of microRNA inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4409.