CaltechAUTHORS
Published May 10, 2012 | Version Accepted Version
Journal Article Open

Systemic delivery of siRNA nanoparticles targeting RRM2 suppresses head and neck tumor growth

Creators

Abstract

Systemic delivery of siRNA to solid tumors remains challenging. In this study, we investigated the systemic delivery of a siRNA nanoparticle targeting ribonucleotide reductase subunit M2 (RRM2), and evaluated its intratumoral kinetics, efficacy and mechanism of action. Knockdown of RRM2 by an RNAi mechanism strongly inhibited cell growth in head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC) cell lines. In a mouse xenograft model of HNSCC, a single intravenous injection led to the accumulation of intact nanoparticles in the tumor that disassembled over a period of at least 3 days, leading to target gene knockdown lasting at least 10 days. A four-dose schedule of siRNA nanoparticle delivering RRM2 siRNA targeted to HNSCC tumors significantly reduced tumor progression by suppressing cell proliferation and inducing apoptosis. These results show promise for the use of RRM2 siRNA-based therapy for HNSCC and possibly NSCLC.

Additional Information

© 2012 Elsevier B.V. Received 9 December 2011. Accepted 27 January 2012. Available online 8 February 2012. This work was supported by NIH/NCI grants U01CA151802 and U54CA119347, P50 CA128613 (Head and Neck Cancer SPORE) and, P30 CA138292. We thank Dr. Anthea Hammond for her critical and editorial review of this article. Dr. Davis has founders stock in Calando Pharmaceuticals and there is no financial conflict of interest to other authors.

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Accepted Version - nihms355935.pdf

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Additional details

Identifiers

PMCID
PMC3348392
Eprint ID
32238
DOI
10.1016/j.jconrel.2012.01.045
Resolver ID
CaltechAUTHORS:20120702-142250235

Related works

Describes
10.1016/j.jconrel.2012.01.045 (DOI)

Funding

NIH
U01CA151802
NIH
U54CA119347
NIH
P50 CA128613
NIH
P30 CA138292

Dates

Created
2012-07-03
Created from EPrint's datestamp field
Updated
2021-11-09
Created from EPrint's last_modified field