Excretable, ultrasmall hexagonal NaGdF4:Yb50% nanoparticles for bimodal imaging and radiosensitization

Jossana A Damasco; Tymish Y Ohulchanskyy; Supriya Mahajan; Guanying Chen; Ajay Singh; Hilliard L Kutscher; Haoyuan Huang; Steven G Turowski; Joseph A Spernyak; Anurag K Singh; Jonathan F Lovell; Mukund Seshadri; Paras N Prasad

doi:10.1186/s12645-021-00075-x

Excretable, ultrasmall hexagonal NaGdF₄:Yb50% nanoparticles for bimodal imaging and radiosensitization

Cancer Nanotechnol. 2021;12(1):4. doi: 10.1186/s12645-021-00075-x. Epub 2021 Feb 5.

Authors

Jossana A Damasco^{1

2}, Tymish Y Ohulchanskyy^{1

3}, Supriya Mahajan⁴, Guanying Chen^{1

5}, Ajay Singh¹, Hilliard L Kutscher^{1

6}, Haoyuan Huang⁷, Steven G Turowski⁸, Joseph A Spernyak⁸, Anurag K Singh⁹, Jonathan F Lovell⁷, Mukund Seshadri^{8

10}, Paras N Prasad¹

Affiliations

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.

Keywords: Gadolinium nanoparticles; Glioblastoma; MR/CT imaging probes; Radiosensitizer; Theranostics.

Grants and funding

KL2 TR001413/TR/NCATS NIH HHS/United States