Versatile RNA Interference Nanoplatform for Systemic Delivery of RNAs
Name
Choi-2014-Versatile RNA.pdf
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6.41 MB
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Checksum (MD5)
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Author(s)
Choi, Ki Young
Silvestre, Oscar F.
Huang, Xinglu
Min, Kyung Hyun
Howard, Gregory P.
Hida, Naoki
Jin, Albert J.
Carvajal, Nicole
Lee, Sang Wook
Hong, Jong-In
Date Issued
April 2014
Journal
ACS Nano
Publisher
American Chemical Society (ACS)
Citation
Choi, Ki Young, Oscar F. Silvestre, Xinglu Huang, Kyung Hyun Min, Gregory P. Howard, Naoki Hida, Albert J. Jin, et al. “Versatile RNA Interference Nanoplatform for Systemic Delivery of RNAs.” ACS Nano 8, no. 5 (May 27, 2014): 4559–4570. © 2014 American Chemical Society
Version
Final published version
Abstract
Development of nontoxic, tumor-targetable, and potent in vivo RNA delivery systems remains an arduous challenge for clinical application of RNAi therapeutics. Herein, we report a versatile RNAi nanoplatform based on tumor-targeted and pH-responsive nanoformulas (NFs). The NF was engineered by combination of an artificial RNA receptor, Zn(II)-DPA, with a tumor-targetable and drug-loadable hyaluronic acid nanoparticle, which was further modified with a calcium phosphate (CaP) coating by in situ mineralization. The NF can encapsulate small-molecule drugs within its hydrophobic inner core and strongly secure various RNA molecules (siRNAs, miRNAs, and oligonucleotides) by utilizing Zn(II)-DPA and a robust CaP coating. We substantiated the versatility of the RNAi nanoplatform by demonstrating effective delivery of siRNA and miRNA for gene silencing or miRNA replacement into different human types of cancer cells in vitro and into tumor-bearing mice in vivo by intravenous administration. The therapeutic potential of NFs coloaded with an anticancer drug doxorubicin (Dox) and multidrug resistance 1 gene target siRNA (siMDR) was also demonstrated in this study. NFs loaded with Dox and siMDR could successfully sensitize drug-resistant OVCAR8/ADR cells to Dox and suppress OVCAR8/ADR tumor cell proliferation in vitro and tumor growth in vivo. This gene/drug delivery system appears to be a highly effective nonviral method to deliver chemo- and RNAi therapeutics into host cells.
MIT Department
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1021/nn500085k
