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Proc Natl Acad Sci U S A. 2016 Jul 12;113(28):7750-5. doi: 10.1073/pnas.1605841113. Epub 2016 Jun 24.

Theranostic near-infrared fluorescent nanoplatform for imaging and systemic siRNA delivery to metastatic anaplastic thyroid cancer.

Author information

1
Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;
2
Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02214.
3
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.
4
Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02214 jshi@bwh.harvard.edu sparangi@partners.org ofarokhzad@bwh.harvard.edu.

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.

KEYWORDS:

NIR imaging; anaplastic thyroid cancer; nanoparticle; siRNA delivery; theranostic

PMID:
27342857
PMCID:
PMC4948349
DOI:
10.1073/pnas.1605841113
[Indexed for MEDLINE]
Free PMC Article

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