title: Theranostic near-infrared fluorescent nanoplatform for imaging and systemic siRNA delivery to metastatic anaplastic thyroid cancer.
abstract: Anaplastic thyroid cancer (ATC), one of the most aggressive solid tumors, is characterized by rapid tumor growth and severe metastasis to other organs. Owing to the lack of effective treatment options, ATC has a mortality rate of ∼100% and median survival of less than 5 months. RNAi nanotechnology represents a promising strategy for cancer therapy through nanoparticle (NP) -mediated delivery of RNAi agents (e.g., siRNA) to solid tumors for specific silencing of target genes driving growth and/or metastasis. Nevertheless, the clinical success of RNAi cancer nanotherapies remains elusive in large part because of the suboptimal systemic siRNA NP delivery to tumors and the fact that tumor heterogeneity produces variable NP accumulation and thus, therapeutic response. To address these challenges, we here present an innovative theranostic NP platform composed of a near-infrared (NIR) fluorescent polymer for effective in vivo siRNA delivery to ATC tumors and simultaneous tracking of the tumor accumulation by noninvasive NIR imaging. The NIR polymeric NPs are small (∼50 nm), show long blood circulation and high tumor accumulation, and facilitate tumor imaging. Systemic siRNA delivery using these NPs efficiently silences the expression of V-Raf murine sarcoma viral oncogene homolog B (BRAF) in tumor tissues and significantly suppresses tumor growth and metastasis in an orthotopic mouse model of ATC. These results suggest that this theranostic NP system could become an effective tool for NIR imaging-guided siRNA delivery for personalized treatment of advanced malignancies.
authors.affiliation: Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;
authors.forename: Yanlan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02214.
authors.forename: Viswanath
authors.initials: V
authors.lastname: Gunda
authors.affiliation: Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;
authors.forename: Xi
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;
authors.forename: Xiaoding
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;
authors.forename: Diana
authors.initials: D
authors.lastname: Askhatova
authors.affiliation: Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115; jshi@bwh.harvard.edu sparangi@partners.org ofarokhzad@bwh.harvard.edu.
authors.forename: Omid C
authors.initials: OC
authors.lastname: Farokhzad
authors.affiliation: Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02214 jshi@bwh.harvard.edu sparangi@partners.org ofarokhzad@bwh.harvard.edu.
authors.forename: Sareh
authors.initials: S
authors.lastname: Parangi
authors.affiliation: Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115; jshi@bwh.harvard.edu sparangi@partners.org ofarokhzad@bwh.harvard.edu.
authors.forename: Jinjun
authors.initials: J
authors.lastname: Shi
mesh_terms: D000818:Animals; D005260:Female; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D008819:Mice, Nude; D016513:Mice, SCID; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry; D061848:Optical Imaging / Q000379:methods*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D000068936:Theranostic Nanomedicine / Q000379:methods*; D065646:Thyroid Carcinoma, Anaplastic / Q000000981:diagnostic imaging / Q000628:therapy*; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D034741:RNA, Small Interfering; C482120:Braf protein, mouse; D048493:Proto-Oncogene Proteins B-raf
keywords: NIR imaging; anaplastic thyroid cancer; nanoparticle; siRNA delivery; theranostic