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.
Document Type
Article
Publication Date
1-2018
Digital Object Identifier (DOI)
https://doi.org/10.1038/s41565-017-0012-z
Funding Information
The research was supported mainly by NIH grants UH3TR000875 and U01CA207946 (P. Guo), and partially by R01CA186100 (B. Guo), R35CA197706 (C.M.C.), P30CA177558 and R01CA195573 (B.M.E.).
Related Content
Supplementary information is available in the online version of the paper.
Repository Citation
Pi, Fengmei; Binzel, Daniel W.; Lee, Tae Jin; Li, Zhefeng; Sun, Meiyan; Rychahou, Piotr G.; Li, Hui; Haque, Farzin; Wang, Shaoying; Croce, Carlo M.; Guo, Bin; Evers, B. Mark; and Guo, Peixuan, "Nanoparticle Orientation to Control RNA Loading and Ligand Display on Extracellular Vesicles for Cancer Regression" (2018). Markey Cancer Center Faculty Publications. 136.
https://uknowledge.uky.edu/markey_facpub/136
Supplementary Information
41565_2017_12_MOESM2_ESM.pdf (99 kB)
Life Sciences Reporting Summary
Notes/Citation Information
Published in Nature Nanotechnology, v. 13, no. 1, p. 82-89.
© 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
The copyright holder has granted the permission for posting the article here.
This is a post-peer-review, pre-copyedit version of an article published in Nature Nanotechnology. The final authenticated version is available online at: https://doi.org/10.1038/s41565-017-0012-z.