Poster abstracts
Poster number 69 submitted by Hui Zhang
RNA nanoparticles harboring annexin A2 aptamer can target ovarian cancer for tumor-specific doxorubicin delivery
Hui Zhang, Fengmei Pi, Hui Li (The Ohio State University), Varatharasa Thiviyanathan (University of Texas Health Science Center), David Gorenstein (University of Texas Health Science Center), Anil Sood (University of Texas MD Anderson Cancer Center), Peixuan Guo (The Ohio State University)
Abstract:
Ovarian cancer is a highly metastatic and lethal disease with the highest mortality rate of all cancers of the female reproductive system. Targeted delivery of therapeutics to cancer cells, with little collateral damage to healthy cells, remains a promising option for the treatment of ovarian cancer. Utilizing the state-of-art RNA nanotechnology platform, we designed and constructed RNA nanoparticles that harbors an annexin A2 aptamer that can target ovarian cancer cells and a GC rich sequence to load doxorubicin (DOX) for ovarian cancer cell targeted drug delivery. The system utilizes a highly stable three-way junction (3WJ) motif from phi29 packaging RNA as a core structure. A phosphorothioate-modified DNA aptamer targeting annexin A2, Endo28, was conjugated to one arm of the 3WJ. The ultrastable pRNA-3WJ motif facilitates the correct folding of attached aptamer, retaining its function for aptamer-mediated targeted delivery. 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 Endo28-3WJ-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 Endo28-3WJ nanoparticle will benefit ovarian cancer patients by reducing the side effects of cancer chemotherapeutics and increasing its local concentration in the tumor microenvironment after systemic administration.
References:
Pi F, Zhang H, Li H, Thiviyanathan V, Gorenstein DG, Sood AK, Guo P. RNA nanoparticles harboring annexin A2 aptamer can target ovarian cancer for tumor-specific doxorubicin delivery. Nanomedicine. 2016. 13(3):1183-1193
Keywords: RNA nanoparticle, pRNA-3WJ, Ovarian cancer