Poster abstracts
Poster number 29 submitted by Zhefeng Li
Nanoparticle orientation to control RNA loading and ligand display on exosome for cancer therapy
Zhefeng Li, Fengmei Pi, Daniel Binzel, Hui Li, Farzin Haque, Shaoying Wang (College of Pharmacy; Center for RNA Nanobiotechnology and Nanomedicine, The Ohio State University, Columbus, OH 43210, USA. ), Tae Jin Lee, Carlo M. Croce (Comprehensive Cancer Center, Department of Cancer Biology and Genetics, College of Medicine; The Ohio State University, Columbus, OH 43210, USA. ), Meiyan Sun, Bin Guo (Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy; University of Houston, Houston, TX 77030, USA.), Piotr Rychahou, B. Mark Evers (Markey Cancer Center; Department of Surgery; University of Kentucky, Lexington, KY 40536, USA. ), Peixuan Guo (College of Pharmacy; Center for RNA Nanobiotechnology and Nanomedicine; Comprehensive Cancer Center, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210)
Abstract:
Nanotechnology offers many benefits, and here we report an advantage of applying RNA nanotechnology to engineer exosome, an extracellular vesicle, for cancer specific delivery of small interfering RNA (siRNA) in vivo. The orientation of arrow-shaped RNA was altered to control ligand display on exosome membranes for specific cell targeting, or cargo loading into exosome. Placing membrane-anchoring cholesterol at the tail of the arrow results in display of RNA aptamer or folate on the outer surface of the exosome. In contrast, placing the cholesterol at the arrowhead results in partial loading of RNA nanoparticles into the exosomes. RNA interference (RNAi) has powerful therapeutic potential for gene therapy, however, delivery is the major barrier for the clinical translation of RNAi. Exosome hold high efficiency in cell fusion and endosome escape, but the lack of specific cell targeting has led to side effect. Taking the advantage of RNA nanotechnology and exosome, this study provides a novel in vivo delivery platform for cancer therapy. Survivin siRNA was used as therapeutic cargo to verify the delivery efficacy on prostate cancer, breast cancer and patient derived colorectal cancer xenograft model. Taking advantage of the RNA ligand for specific targeting and exosome for efficient membrane fusion and endosome escape, the resulting ligand-displaying exosomes were capable of specific delivery of siRNA to cells, and efficiently blocked tumor growth in breast cancer, brain cancer, and prostate cancer models. Exosomes displaying an aptamer that binds to prostate-specific membrane antigen, and loaded with survivin siRNA, inhibited prostate cancer xenograft. The same exosomes instead displaying epidermal growth-factor receptor aptamer inhibited orthotropic breast cancer models. Likewise, survivin siRNA-loaded and folate-displaying extracellular vesicles inhibited patient-derived colorectal cancer xenograft.
References:
Pi F, Binzel D, Lee TJ, Li Z, Sun M, Rychahou P, Li H, Haque F, Wang S, Croce CM, Guo B, Evers BM,Guo P. Nanoparticle orientation to control RNA loading and ligand display on extracellular vesicles for cancer regression. Nature Nanotechnology. 2018 Jan; 13(1):82-89.
Keywords: RNA nanotechnology, Exosome, siRNA delivery