Engineered polymeric nanoparticles to guide the cellular internalization and trafficking of small interfering ribonucleic acids

Amy E Arnold; Petro Czupiel; Molly Shoichet

doi:10.1016/j.jconrel.2017.02.019

Engineered polymeric nanoparticles to guide the cellular internalization and trafficking of small interfering ribonucleic acids

J Control Release. 2017 Aug 10:259:3-15. doi: 10.1016/j.jconrel.2017.02.019. Epub 2017 Feb 21.

Authors

Amy E Arnold¹, Petro Czupiel², Molly Shoichet³

Affiliations

¹ Department of Chemistry, University of Toronto, 80 St George Street, Toronto, ON, M5S 3H6, Canada; Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON, M5S 3E1, Canada.
² Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON, M5S 3E5, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON, M5S 3G9, Canada; Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON, M5S 3E1, Canada.
³ Department of Chemistry, University of Toronto, 80 St George Street, Toronto, ON, M5S 3H6, Canada; Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON, M5S 3E5, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, 164 College Street, Toronto, ON, M5S 3G9, Canada; Donnelly Centre, University of Toronto, 160 College Street, Toronto, ON, M5S 3E1, Canada. Electronic address: molly.shoichet@utoronto.ca.

PMID: 28232223
DOI: 10.1016/j.jconrel.2017.02.019

Abstract

Ribonucleic acid interference therapy is a promising cancer treatment, which uses small interfering RNAs (siRNAs) to target and degrade messenger RNAs. Due to endogenous nuclease activity, siRNA is degraded rapidly, resulting in poor cell uptake and hence specificity. Moreover, it will not readily cross the cell membrane by passive diffusion. In order to take advantage of the therapeutic power of siRNA for the treatment of cancer, specialized delivery vehicles have been designed. In this review, we highlight advances in optimizing nanoparticle functionalization for guided siRNA delivery at the cellular level - that is, promoting cell uptake, escaping the endosome, and releasing siRNA from the delivery vehicle.

Keywords: Cancer therapeutics; Drug delivery; Nanoparticles; Polymers; Trafficking; siRNA.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Biological Transport
Endosomes / metabolism
Humans
Lysosomes / metabolism
Nanoparticles / administration & dosage*
Polymers / administration & dosage
RNA, Small Interfering / administration & dosage*

Substances

Polymers
RNA, Small Interfering

Grants and funding

FDN-143276/CIHR/Canada