Dual bioluminescence and near-infrared fluorescence monitoring to evaluate spherical nucleic acid nanoconjugate activity in vivo
Abstract
Small interfering (si) and micro (mi)RNA-carrying nanomaterials emerged as a new class of anticancer therapeutics. To enable quantification of intratumoral gene expression in response to RNAi nanoconjugate treatment in vivo, we developed a dual reporter glioblastoma xenograft model using cell lines that stably coexpress optical reporters for luciferase and a near-infrared fluorescent protein (iRFP670). We generated orthotopic glioblastoma multiforme tumors expressing an iRFP670-O 6 -methylguanine-DNA-methyltransferase (MGMT) fusion protein for real-time assessment of MGMT-targeting spherical nucleic acids (i.e., gold-based nanoconjugates functionalized with siRNA oligonucleotides targeted to MGMT). We demonstrate that dual noninvasive bioluminescence and fluorescence imaging can determine intratumoral protein expression in response to systemic spherical nucleic acid treatment and represents an in vivo testing platform to facilitate preclinical investigations of nanoscale gene silencing therapeutics.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 03, 2017
- Source ID
- 10.1073/pnas.1702736114
Entities
People
- Alexander H. Stegh
- Alexandra Chalastanis
- Andrew R Lee
- Anthony J. Sprangers
- Chad Mirkin
- Charles David James
- Fotini M. Kouri
- Jasmine L. May
- Lisa A. Hurley
- Lisa E. Cole
- Nikunjkumar Savalia
- Serena T. Ghelfi
- Stacey N. Barnaby
- Thomas C. Cayton
- Timothy J. Merkel
- Timothy L. Sita
Organizations
- National Cancer Institute
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- National Institutes of Health
- Northwestern University