Micron-sized iron oxide-containing particles for microRNA-targeted manipulation and MRI-based tracking of transplanted cells
2015
Leder, Annekatrin | Raschzok, Nathanael | Schmidt, Christian | Arabacioglu, Duygu | Butter, Antje | Kolano, Susanne | de Sousa Lisboa, Luisa S. | Werner, Wiebke | Polenz, Dietrich | Reutzel-Selke, Anja | Pratschke, Johann | Sauer, Igor M.
Particle-based delivery systems for therapeutic manipulation and tracking of transplanted cells by magnetic resonance imaging (MRI) are commonly based on nanometer-sized superparamagnetic iron oxide particles (SPIOs). Here, we present a proof of concept for multifunctional, silica based micron-sized iron oxide-containing particles (sMPIO) that combine fluorescence imaging, MRI tracking, and on-the-spot targeting of specific microRNAs on a particle surface for therapeutic manipulation by RNA interference. Antisense locked nucleic acids (α-LNA) were covalently bound to the surface of silica-based, DAPI-integrated, micron-sized iron oxide particles (sMPIO-α-LNA). In vitro studies using primary human hepatocytes showed rapid particle uptake (4 h) that was accompanied by significant depletion of the targeted microRNA Let7g (80%), up-regulation of the target proteins Cyclin D1 and c-Myc, and specific proteome changes. sMPIO-α-LNA-labeled cells were successfully detected by fluorescence imaging and could be visualized by MRI after intrasplenic transplantation in rats. This new theranostic particle provides a promising tool for cell transplantation where cellular imaging and microRNA-based manipulation is needed. [165]
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