Abstract NT-112: APTAMER CONJUGATED NANOPARTICLES FOR TARGETED DRUG DELIVERY

Abstract

Abstract Targeted Delivery of therapeutic drugs and imaging agents, using nanoparticles, shows great promise in diverse fields, including the diagnostics and treatment of cancer. Monoclonal antibodies (mAbs) that have been traditionally used for detecting specific proteins can also be used as targeting moieties. However, due to their intrinsic characteristics such as immunogenicity, batch-to-batch variation and instability, antibodies have several limitations for in vivo applications. Nucleic acid based aptamers are emerging as attractive alternatives for mAbs. We have developed single-stranded DNA aptamers, which can specifically recognize and bind to ovarian cancer endothelial cells. Using mass-spectroscopy based proteomics, we have identified Annexin A2 as the protein target for the selected aptamers. These aptamers can act as homing devices to deliver therapeutic drugs and/or imaging agents specifically to ovarian cancer cells. Using a highly stable, three-way junction (3WJ) motif from the phi29 packaging RNA as a scaffold, we made a multi-functional RNA nanoparticle that can harbor therapeutic drugs, imaging agent, siRNA and the targeting ligand. The aptamer-containing multi-functional RNA nanoparticle is used to deliver Doxorubicin to Annexin A2 positive ovarian cancer cells, while the control nanoparticles failed to deliver. After systemic injection in mice, the DNA/RNA hybrid nanoparticles remained intact and strongly bound to tumors with little accumulation in healthy organs 6 hour post-injection. The aptamer-3WJ-Sph1/Dox intercalates selectively enhanced toxicity to Annexin A2 positive ovarian cancer cells in vitro, demonstrating the potential of the constructed DNA/RNA hybrid nanoparticles to enhance the therapeutic efficiency of Doxorubicin at low doses for ovarian cancer treatment. The use of the aptamer-3WJ RNA nanoparticle will benefit ovarian cancer patients by reducing the side effects of cancer chemo-therapeutics and increasing its local concentration in the tumor microenvironment after systemic administration. Our ultimate goal is the development of patient-optimized aptamer-nanoparticle delivery systems for chemotherapy and molecular diagnostics imaging. Citation Format: Varatharasa Thiviyanathan, Fengmei Pi, Hui Zhang, Hui Li , Hongyu Wang, Peixuan Guo, Anil Sood. APTAMER CONJUGATED NANOPARTICLES FOR TARGETED DRUG DELIVERY [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr NT-112.