Micron-sized iron oxide-containing particles for microRNA-targeted manipulation and MRI-based tracking of transplanted cells

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 (alpha-LNA) were covalently bound to the surface of silica-based, DAPI-integrated, micron-sized iron oxide particles (sMPIO-alpha-LNA). In vitro studies using primary human hepatocytes showed rapid particle uptake (4 h) that was accompanied by significant depletion of the targeted microRNA Let 7g (80%), up-regulation of the target proteins Cyclin D1 and c-Myc, and specific proteome changes. sMPIO-alpha-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] (C) 2015 Elsevier Ltd. All rights reserved.