Open Access<p>Highly sensitive electron paramagnetic resonance nanoradicals for quantitative intracellular tumor oxymetric images</p>
Author(s) -
Nai-Tzu Chen,
Eugene D. Barth,
Tsung-Hsi Lee,
Chin-Tu Chen,
Boris Epel,
Howard J. Halpern,
LeuWei Lo
Publication year - 2019
Publication title -
international journal of nanomedicine
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 1.245
H-Index - 128
eISSN - 1178-2013
pISSN - 1176-9114
DOI - 10.2147/ijn.s194779
Subject(s) - intracellular , nuclear magnetic resonance , electron paramagnetic resonance , magnetic resonance imaging , materials science , electron paramagnetic resonance spectroscopy , biophysics , chemistry , medicine , physics , biology , biochemistry , radiology
Purpose: Tumor oxygenation is a critical parameter influencing the efficacy of cancer therapy. Low levels of oxygen in solid tumor have been recognized as an indicator of malignant progression and metastasis, as well as poor response to chemo- and radiation therapy. Being able to measure oxygenation for an individual's tumor would provide doctors with a valuable way of identifying optimal treatments for patients. Methods: Electron paramagnetic resonance imaging (EPRI) in combination with an oxygen-measuring paramagnetic probe was performed to measure tumor oxygenation in vivo. Triarylmethyl (trityl) radical exhibits high specificity, sensitivity, and resolution for quantitative measurement of O 2 concentration. However, its in vivo applications in previous studies have been limited by the required high dosage, its short half-life, and poor intracellular permeability. To address these limitations, we developed high-capacity nanoformulated radicals that employed fluorescein isothiocyanate-labeled mesoporous silica nanoparticles (FMSNs) as trityl radical carriers. The high surface area nanostructure and easy surface modification of physiochemical properties of FMSNs enable efficient targeted delivery of highly concentrated, nonself-quenched trityl radicals, protected from environmental degradation and dilution. Results: We successfully designed and synthesized a tumor-targeted nanoplatform as a carrier for trityl. In addition, the nanoformulated trityl does not affect oxygen-sensing capacity by a self-relaxation or broadening effect. The FMSN-trityl exhibited high sensitivity/response to oxygen in the partial oxygen pressure range from 0 to 155 mmHg. Furthermore, MSN-trityl displayed outstanding intracellular oxygen mapping in both in vitro and in vivo animal studies. Conclusion: The highly sensitive nanoformulated trityl spin probe can profile intracellular oxygen distributions of tumor in a real-time and quantitative manner using in vivo EPRI.