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

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

doi:10.1016/j.jconrel.2012.01.045

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

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

Research output: Contribution to journal › Article

60 Citations (Scopus)

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	https://doi.org/10.1016/j.jconrel.2012.01.045
Publication status	Published - May 10 2012
Externally published	Yes

Keywords

RNA interference
RRM2
SiRNA delivery
Targeted nanoparticle
TfR
Tumor growth

ASJC Scopus subject areas

Pharmaceutical Science

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Rahman, M. A., Amin, A. R. M. R., Wang, X., Zuckerman, J. E., Choi, C. H. J., Zhou, B., Wang, D., Nannapaneni, S., Koenig, L., Chen, Z., Chen, Z. G., Yen, Y., Davis, M. E., & Shin, D. M. (2012). Systemic delivery of siRNA nanoparticles targeting RRM2 suppresses head and neck tumor growth. Journal of Controlled Release, 159(3), 384-392. https://doi.org/10.1016/j.jconrel.2012.01.045

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

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. / Systemic delivery of siRNA nanoparticles targeting RRM2 suppresses head and neck tumor growth. In: Journal of Controlled Release. 2012 ; Vol. 159, No. 3. pp. 384-392.

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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.

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