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

Rahman, Mohammad Aminur and Amin, A. R. M. Ruhul and Wang, Xu and Zuckerman, Jonathan E. and Choi, Chung Hang J. and Zhou, Bingsen and Wang, Dongsheng and Nannapaneni, Sreenivas and Koenig, Lydia and Chen, Zhengjia and Chen, Zhuo (Georgia) and Yen, Yun and Davis, Mark E. and Shin, Dong M. (2012) Systemic delivery of siRNA nanoparticles targeting RRM2 suppresses head and neck tumor growth. Journal of Controlled Release, 159 (3). pp. 384-392. ISSN 0168-3659. PMCID PMC3348392. https://resolver.caltech.edu/CaltechAUTHORS:20120702-142250235

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.jconrel.2012.01.045DOIArticle
http://www.sciencedirect.com/science/article/pii/S0168365912000776PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3348392PubMed CentralArticle
ORCID:
AuthorORCID
Yen, Yun0000-0003-0815-412X
Davis, Mark E.0000-0001-8294-1477
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.
Funders:
Funding AgencyGrant Number
NIHU01CA151802
NIHU54CA119347
NIHP50 CA128613
NIHP30 CA138292
Subject Keywords:SiRNA delivery; Targeted nanoparticle; RNA interference; RRM2; TfR; Tumor growth
Issue or Number:3
PubMed Central ID:PMC3348392
Record Number:CaltechAUTHORS:20120702-142250235
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20120702-142250235
Official Citation:Mohammad Aminur Rahman, A.R.M. Ruhul Amin, Xu Wang, Jonathan E. Zuckerman, Chung Hang J. Choi, Bingsen Zhou, Dongsheng Wang, Sreenivas Nannapaneni, Lydia Koenig, Zhengjia Chen, Zhuo (Georgia) Chen, Yun Yen, Mark E. Davis, Dong M. Shin, Systemic delivery of siRNA nanoparticles targeting RRM2 suppresses head and neck tumor growth, Journal of Controlled Release, Volume 159, Issue 3, 10 May 2012, Pages 384-392, ISSN 0168-3659, 10.1016/j.jconrel.2012.01.045.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:32238
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:03 Jul 2012 14:32
Last Modified:20 Nov 2019 20:30

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