title: Systemic delivery of siRNA nanoparticles targeting RRM2 suppresses head and neck tumor growth.
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 3days, leading to target gene knockdown lasting at least 10days. 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.
authors.affiliation: Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors.forename: Mohammad Aminur
authors.initials: MA
authors.lastname: Rahman
authors.forename: A R M Ruhul
authors.initials: AR
authors.lastname: Amin
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Zuckerman
authors.forename: Chung Hang J
authors.initials: CH
authors.lastname: Choi
authors.forename: Bingsen
authors.initials: B
authors.lastname: Zhou
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Wang
authors.forename: Sreenivas
authors.initials: S
authors.lastname: Nannapaneni
authors.forename: Lydia
authors.initials: L
authors.lastname: Koenig
authors.forename: Zhengjia
authors.initials: Z
authors.lastname: Chen
authors.forename: Zhuo Georgia
authors.initials: ZG
authors.lastname: Chen
authors.forename: Yun
authors.initials: Y
authors.lastname: Yen
authors.forename: Mark E
authors.initials: ME
authors.lastname: Davis
authors.forename: Dong M
authors.initials: DM
authors.lastname: Shin
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D051379:Mice; D008819:Mice, Nude; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D012262:Ribonucleoside Diphosphate Reductase / Q000037:antagonists & inhibitors* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D034741:RNA, Small Interfering; C093713:ribonucleotide reductase M2; D012262:Ribonucleoside Diphosphate Reductase