Jossana A Damasco1,2, Tymish Y Ohulchanskyy1,3, Supriya Mahajan4, Guanying Chen1,5, Ajay Singh1, Hilliard L Kutscher1,6, Haoyuan Huang7, Steven G Turowski8, Joseph A Spernyak8, Anurag K Singh9, Jonathan F Lovell7, Mukund Seshadri8,10, Paras N Prasad1. 1. Department of Chemistry and Institute for Lasers, Photonics and Biophotonics, University At Buffalo, The State University of New York, Buffalo, NY 14260 USA. 2. Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 USA. 3. College of Optoelectronic Engineering, College of Physics and Optoelectronic Engineering, Shenzhen University, 518060 Shenzhen, People's Republic of China. 4. Department of Medicine, Division of Allergy, Immunology and Rheumatology, University At Buffalo, The State University of New York, Buffalo, NY 14203 USA. 5. School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, Heilongjiang 15001 People's Republic of China. 6. Department of Anesthesiology, University At Buffalo, The State University of New York, Buffalo, NY 14214 USA. 7. Department of Biomedical Engineering, University At Buffalo, The State University of New York, Buffalo, NY 14260 USA. 8. Translational Imaging Shared Resource, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263 USA. 9. Department of Radiation Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263 USA. 10. Department of Oral Oncology/Dentistry and Maxillofacial Prosthetics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263 USA.
Abstract
BACKGROUND: In this study, we report on the synthesis, imaging, and radiosensitizing properties of ultrasmall β-NaGdF4:Yb50% nanoparticles as a multifunctional theranostic platform. The synthesized nanoparticles act as potent bimodal contrast agents with superior imaging properties compared to existing agents used for magnetic resonance imaging (MRI) and computed tomography (CT). Clonogenic assays demonstrated that these nanoparticles can act as effective radiosensitizers, provided that the nanoparticles are taken up intracellularly. RESULTS: Our ultrasmall β-NaGdF4:Yb50% nanoparticles demonstrate improvement in T1-weighted contrast over the standard clinical MR imaging agent Gd-DTPA and similar CT signal enhancement capabilities as commercial agent iohexol. A 2 Gy dose of X-ray induced ~ 20% decrease in colony survival when C6 rat glial cells were incubated with non-targeted nanoparticles (NaGdF4:Yb50%), whereas the same X-ray dose resulted in a ~ 60% decrease in colony survival with targeted nanoparticles conjugated to folic acid (NaGdF4:Yb50%-FA). Intravenous administration of nanoparticles resulted in clearance through urine and feces within a short duration, based on the ex vivo analysis of Gd3+ ions via ICP-MS. CONCLUSION: These biocompatible and in vivo clearable ultrasmall NaGdF4:Yb50% are promising candidates for further evaluation in image-guided radiotherapy applications.
BACKGROUND: In this study, we report on the synthesis, imaging, and radiosensitizing properties of ultrasmall β-NaGdF4:Yb50% nanoparticles as a multifunctional theranostic platform. The synthesized nanoparticles act as potent bimodal contrast agents with superior imaging properties compared to existing agents used for magnetic resonance imaging (MRI) and computed tomography (CT). Clonogenic assays demonstrated that these nanoparticles can act as effective radiosensitizers, provided that the nanoparticles are taken up intracellularly. RESULTS: Our ultrasmall β-NaGdF4:Yb50% nanoparticles demonstrate improvement in T1-weighted contrast over the standard clinical MR imaging agent Gd-DTPA and similar CT signal enhancement capabilities as commercial agent iohexol. A 2 Gy dose of X-ray induced ~ 20% decrease in colony survival when C6 rat glial cells were incubated with non-targeted nanoparticles (NaGdF4:Yb50%), whereas the same X-ray dose resulted in a ~ 60% decrease in colony survival with targeted nanoparticles conjugated to folic acid (NaGdF4:Yb50%-FA). Intravenous administration of nanoparticles resulted in clearance through urine and feces within a short duration, based on the ex vivo analysis of Gd3+ ions via ICP-MS. CONCLUSION: These biocompatible and in vivo clearable ultrasmall NaGdF4:Yb50% are promising candidates for further evaluation in image-guided radiotherapy applications.
Authors: Neus Feliu; Dominic Docter; Markus Heine; Pablo Del Pino; Sumaira Ashraf; Jelena Kolosnjaj-Tabi; Paolo Macchiarini; Peter Nielsen; Damien Alloyeau; Florence Gazeau; Roland H Stauber; Wolfgang J Parak Journal: Chem Soc Rev Date: 2016-05-03 Impact factor: 54.564