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Nat Nanotechnol. 2018 Jan;13(1):82-89. doi: 10.1038/s41565-017-0012-z. Epub 2017 Dec 11.

Nanoparticle orientation to control RNA loading and ligand display on extracellular vesicles for cancer regression.

Pi F1,2,3,4, Binzel DW1,2,3,4, Lee TJ3,5,6, Li Z1,2,3,4, Sun M7, Rychahou P8, Li H1,2,3,4, Haque F1,2,3,4, Wang S1,2,3,4, Croce CM3,5, Guo B7, Evers BM8, Guo P9,10,11,12,13.

Author information

1
College of Pharmacy, The Ohio State University, Columbus, OH, USA.
2
Center for RNA Nanobiotechnology and Nanomedicine, The Ohio State University, Columbus, OH, USA.
3
Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
4
Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
5
Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University, Columbus, OH, USA.
6
Department of Neurosurgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
7
Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, USA.
8
Markey Cancer Center, Department of Surgery, University of Kentucky, Lexington, KY, USA.
9
College of Pharmacy, The Ohio State University, Columbus, OH, USA. guo.1091@osu.edu.
10
Center for RNA Nanobiotechnology and Nanomedicine, The Ohio State University, Columbus, OH, USA. guo.1091@osu.edu.
11
Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA. guo.1091@osu.edu.
12
Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA. guo.1091@osu.edu.
13
Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University, Columbus, OH, USA. guo.1091@osu.edu.

Abstract

Nanotechnology offers many benefits, and here we report an advantage of applying RNA nanotechnology for directional control. The orientation of arrow-shaped RNA was altered to control ligand display on extracellular vesicle membranes for specific cell targeting, or to regulate intracellular trafficking of small interfering RNA (siRNA) or microRNA (miRNA). Placing membrane-anchoring cholesterol at the tail of the arrow results in display of RNA aptamer or folate on the outer surface of the extracellular vesicle. In contrast, placing the cholesterol at the arrowhead results in partial loading of RNA nanoparticles into the extracellular vesicles. Taking advantage of the RNA ligand for specific targeting and extracellular vesicles for efficient membrane fusion, the resulting ligand-displaying extracellular vesicles were capable of specific delivery of siRNA to cells, and efficiently blocked tumour growth in three cancer models. Extracellular vesicles displaying an aptamer that binds to prostate-specific membrane antigen, and loaded with survivin siRNA, inhibited prostate cancer xenograft. The same extracellular vesicle instead displaying epidermal growth-factor receptor aptamer inhibited orthotopic breast cancer models. Likewise, survivin siRNA-loaded and folate-displaying extracellular vesicles inhibited patient-derived colorectal cancer xenograft.

PMID:
29230043
PMCID:
PMC5762263
DOI:
10.1038/s41565-017-0012-z
[Indexed for MEDLINE]
Free PMC Article

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