Porous silicon-graphene oxide core-shell nanoparticles for targeted delivery of siRNA to the injured brain

Jinmyoung Joo; Ester J Kwon; Jinyoung Kang; Matthew Skalak; Emily J Anglin; Aman P Mann; Erkki Ruoslahti; Sangeeta N Bhatia; Michael J Sailor

doi:10.1039/C6NH00082G

Porous silicon-graphene oxide core-shell nanoparticles for targeted delivery of siRNA to the injured brain

Nanoscale Horiz. 2016 Sep 1;1(5):407-414. doi: 10.1039/C6NH00082G. Epub 2016 Jun 14.

Authors

Jinmyoung Joo¹, Ester J Kwon², Jinyoung Kang³, Matthew Skalak², Emily J Anglin¹, Aman P Mann⁴, Erkki Ruoslahti^{4

5}, Sangeeta N Bhatia^{2

6

7

8

9

10}, Michael J Sailor^{1

3}

Affiliations

¹ Department of Chemistry, University of California, San Diego, La Jolla, CA 92093, USA.
² Harvard-MIT Division of Health Science and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
³ Department of Nanoengineering, University of California, San Diego, La Jolla, CA 92093, USA.
⁴ Cancer Research Center, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
⁵ Center for Nanomedicine and Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
⁶ Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁷ David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁸ Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
⁹ Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
¹⁰ Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

Abstract

We report the synthesis, characterization, and assessment of a nanoparticle-based RNAi delivery platform that protects siRNA payloads against nuclease-induced degradation and efficiently delivers them to target cells. The nanocarrier is based on biodegradable mesoporous silicon nanoparticles (pSiNPs), where the voids of the nanoparticles are loaded with siRNA and the nanoparticles are encapsulated with graphene oxide nanosheets (GO-pSiNPs). The graphene oxide encapsulant delays release of the oligonucleotide payloads in vitro by a factor of 3. When conjugated to a targeting peptide derived from the rabies virus glycoprotein (RVG), the nanoparticles show 2-fold greater cellular uptake and gene silencing. Intravenous administration of the nanoparticles into brain-injured mice results in substantial accumulation specifically at the site of injury.

Abstract

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