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 journalArticle

57 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 languageEnglish
Pages (from-to)384-392
Number of pages9
JournalJournal of Controlled Release
Volume159
Issue number3
DOIs
Publication statusPublished - May 10 2012
Externally publishedYes

Fingerprint

Nanoparticles
Small Interfering RNA
Neck
Head
Growth
Neoplasms
Non-Small Cell Lung Carcinoma
Gene Knockdown Techniques
RNA Interference
Heterografts
Intravenous Injections
Appointments and Schedules
Cell Proliferation
ribonucleotide reductase M2
Apoptosis
Cell Line
Carcinoma, squamous cell of head and neck
Therapeutics

Keywords

  • RNA interference
  • RRM2
  • SiRNA delivery
  • Targeted nanoparticle
  • TfR
  • Tumor growth

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Rahman, M. A., Amin, A. R. M. R., Wang, X., Zuckerman, J. E., Choi, C. H. J., Zhou, B., ... 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 journalArticle

Rahman, MA, Amin, ARMR, Wang, X, Zuckerman, JE, Choi, CHJ, Zhou, B, Wang, D, Nannapaneni, S, Koenig, L, Chen, Z, Chen, ZG, Yen, Y, Davis, ME & Shin, DM 2012, 'Systemic delivery of siRNA nanoparticles targeting RRM2 suppresses head and neck tumor growth', Journal of Controlled Release, vol. 159, no. 3, pp. 384-392. https://doi.org/10.1016/j.jconrel.2012.01.045
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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