Electron Paramagnetic Resonance Nanoradicals for Quantitative Intracellular Tumor Oximetric Images
Session Number
Project ID: MEDH 30
Advisor(s)
Dr. Chin-Tu Chen, University of Chicago
Discipline
Medical and Health Sciences
Start Date
17-4-2024 8:55 AM
End Date
17-4-2024 9:10 AM
Abstract
In large solid tumors, a hypoxic core often indicates malignant progression, metastasis, and reduced responsiveness to chemotherapy and radiation. Personalized treatments can benefit from precise measurements of tumor oxygenation and reoxygenation of the tumor. Electron Paramagnetic Resonance Imaging (EPRI) along with an oxygen-measuring paramagnetic probe were used to assess tumor oxygenation in vivo. Triarylmethyl (trityl) radical has been known for its specificity, sensitivity, and resolution in quantifying oxygen concentration, but previous in vivo applications faced challenges from high dosage requirements, short half-life, and poor intracellular permeability. To overcome this, fluorescein isothiocyanate-labeled mesoporous silica nanoparticles (FMSNs) were developed as carriers. Their structure allows for efficient targeted delivery of the trityl radicals while providing protection against environmental degradation and dilution. The tumor-targeted nano platform was successfully designed and synthesized, without compromising oxygen-sensing capacity due to self-relaxation or broadening effects. FMSN-trityl exhibited high sensitivity to oxygen within a partial oxygen pressure range of 0 to 155 mmHg. MSN-trityl demonstrated outstanding intracellular oxygen mapping in both in vitro and in vivo studies. The highly sensitive nanoformulated trityl spin probe enables real-time and quantitative profiling of intracellular tumor oxygen distributions using in vivo EPRI. MSN-trityl provides high-value oxygenation information for in-situ diagnostic imaging in potential clinical applications.
Electron Paramagnetic Resonance Nanoradicals for Quantitative Intracellular Tumor Oximetric Images
In large solid tumors, a hypoxic core often indicates malignant progression, metastasis, and reduced responsiveness to chemotherapy and radiation. Personalized treatments can benefit from precise measurements of tumor oxygenation and reoxygenation of the tumor. Electron Paramagnetic Resonance Imaging (EPRI) along with an oxygen-measuring paramagnetic probe were used to assess tumor oxygenation in vivo. Triarylmethyl (trityl) radical has been known for its specificity, sensitivity, and resolution in quantifying oxygen concentration, but previous in vivo applications faced challenges from high dosage requirements, short half-life, and poor intracellular permeability. To overcome this, fluorescein isothiocyanate-labeled mesoporous silica nanoparticles (FMSNs) were developed as carriers. Their structure allows for efficient targeted delivery of the trityl radicals while providing protection against environmental degradation and dilution. The tumor-targeted nano platform was successfully designed and synthesized, without compromising oxygen-sensing capacity due to self-relaxation or broadening effects. FMSN-trityl exhibited high sensitivity to oxygen within a partial oxygen pressure range of 0 to 155 mmHg. MSN-trityl demonstrated outstanding intracellular oxygen mapping in both in vitro and in vivo studies. The highly sensitive nanoformulated trityl spin probe enables real-time and quantitative profiling of intracellular tumor oxygen distributions using in vivo EPRI. MSN-trityl provides high-value oxygenation information for in-situ diagnostic imaging in potential clinical applications.