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.
| Original language | English |
|---|---|
| Pages (from-to) | 384-392 |
| Number of pages | 9 |
| Journal | Journal of Controlled Release |
| Volume | 159 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - May 10 2012 |
| Externally published | Yes |
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Keywords
- RNA interference
- RRM2
- SiRNA delivery
- Targeted nanoparticle
- TfR
- Tumor growth
ASJC Scopus subject areas
- Pharmaceutical Science
Cite this
Systemic delivery of siRNA nanoparticles targeting RRM2 suppresses head and neck tumor growth. / Rahman, Mohammad Aminur; Amin, A. R.M.Ruhul; Wang, Xu; Zuckerman, Jonathan E.; Choi, Chung Hang J.; Zhou, Bingsen; Wang, Dongsheng; Nannapaneni, Sreenivas; Koenig, Lydia; Chen, Zhengjia; Chen, Zhuo Georgia; Yen, Yun; Davis, Mark E.; Shin, Dong M.
In: Journal of Controlled Release, Vol. 159, No. 3, 10.05.2012, p. 384-392.Research output: Contribution to journal › Article
}
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.
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
VL - 159
SP - 384
EP - 392
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 3
ER -