TY - JOUR
T1 - Systemic delivery of siRNA nanoparticles targeting RRM2 suppresses head and neck tumor growth
AU - Rahman, Mohammad Aminur
AU - Amin, A. R.M.Ruhul
AU - Wang, Xu
AU - Zuckerman, Jonathan E.
AU - Choi, Chung Hang J.
AU - Zhou, Bingsen
AU - Wang, Dongsheng
AU - Nannapaneni, Sreenivas
AU - Koenig, Lydia
AU - Chen, Zhengjia
AU - Chen, Zhuo Georgia
AU - Yen, Yun
AU - Davis, Mark E.
AU - Shin, Dong M.
N1 - Funding Information:
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.
PY - 2012/5/10
Y1 - 2012/5/10
N2 - 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.
AB - 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.
KW - RNA interference
KW - RRM2
KW - SiRNA delivery
KW - Targeted nanoparticle
KW - TfR
KW - Tumor growth
UR - http://www.scopus.com/inward/record.url?scp=84862799430&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862799430&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2012.01.045
DO - 10.1016/j.jconrel.2012.01.045
M3 - Article
C2 - 22342644
AN - SCOPUS:84862799430
VL - 159
SP - 384
EP - 392
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 3
ER -