99m Tc-labeled aminosilane-coated iron oxide nanoparticles for molecular imaging of ανβ3 -mediated tumor expression and feasibility for hyperthermia treatment (original) (raw)

2014, Journal of Colloid and Interface Science

Hypothesis: Dual-modality imaging agents, such as radiolabeled iron oxide nanoparticles (IO-NPs), are promising candidates for cancer diagnosis and therapy. We developed and evaluated aminosilane coated Fe 3 O 4 (10 ± 2 nm) as a tumor imaging agent in nuclear medicine through 3-aminopropyltriethoxysilane (APTES) functionalization. We evaluated this multimeric system of targeted 99m Tc-labeled nanoparticles (NPs) conjugated with a new RGD derivate (cRGDfK-Orn 3-CGG), characterized as NPs-RGD as a potential thermal therapy delivery vehicle. Experiments: Transmission Electron Microscopy (TEM) and spectroscopy techniques were used to characterize the IO-NPs indicating their functionalization with peptides. Radiolabeled IO-NPs (targeted, non-targeted) were evaluated with regard to their radiochemical, radiobiological and imaging characteristics. In vivo studies were performed in normal and a m b 3-positive tumor (U87MG glioblastoma) bearing mice. We also demonstrated that this system could reach ablative temperatures in vivo. Findings: Both radiolabeled IO-NPs were obtained in high radiochemical yield (>98%) and proved stable in vitro. The in vivo studies for both IO-NPs have shown significant liver and spleen uptake at all examined time points in normal and U87MG glioblastoma tumor-bearing mice, due to their colloidal nature. We have confirmed through in vivo biodistribution studies that the non-targeted 99m Tc-NPs poorly internalized in the tumor, while the targeted 99m Tc-NPs-RGD, present 9-fold higher tumor accumulation at 1 h p.i. Accumulation of both IO-NPs in other organs was negligible. Blocking experiments indicated target specificity for integrin receptors in U87MG glioblastoma cells. The preliminary in vivo study of applied alternating magnetic field showed that the induced hyperthermia is feasible due to the aid of IO-NPs.

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