Highly sensitive electron paramagnetic resonance nanoradicals for quantitative intracellular tumor oxymetric images.

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 O2 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.

In-situ formation and assembly of gold nanoparticles by gum arabic as efficient photothermal agent for killing cancer cells.

Gold nanoparticles (AuNPs) have been established to sufficiently eradicate tumors by means of heat production for photothermal therapy. However, the translation of the AuNPs from bench to the clinic still remains to be solved until realizing high bioclearance after treatment. Herein, we developed a simple strategy for simultaneous formation and assembly of small-size gold nanoparticles (Au-SNPs) to form a novel nanocomposite in the presence of gum arabic (GA) by synchrotron X-ray irradiation in an aqueous solution within 5 min. GA, a porous polysaccharide, can not only provide a confined space in which to produce uniform Au-SNPs (1.6 ± 0.7 nm in diameter), but can also facilitate the formation of Au-SNPs@GA (diameter ≈ 40 nm) after irradiating synchrotron X-rays. Specifically, the Au-SNPs@GA possesses high thermal stability and a strong photothermal effect for killing cancer cells. Importantly, a bioclearance study demonstrated that the Au-SNPs@GA can be gradually excreted by the renal and hepatobiliary system, which might be due to the breakdown and oxidation of GA under irradiating synchrotron X-rays. Thus, the novel gold nanocomposite can be promising photothermal agents for cancer treatment at the therapeutic level, minimizing toxicity concerns regarding long-term accumulation in vivo.