Development of gene delivery carrier and molecular imaging system based on inorganic nanoparticles

Abstract

Pluronic/polyethylenimine shell cross-linked nanocapsules with embedded magnetite nanocrystals (PPMCs) were developed for magnetically triggered delivery of small interfering RNA (siRNA). Monodisperse oleic acid-coated iron oxide nanocrystals were successfully encapsulated in a hollow interior space of the nano-capsules surrounded with a cross-linked polymeric shell layer. The positively charged PPMCs formed stable nanosized polyelectrolyte complexes via electrostatic interactions with negatively charged siRNA-polyethylene glycol (PEG) conjugate (siRNA-s-s-PEG) that was linked via a cleavable disulfide linkage. Prussian blue staining and fluorescence images showed that PPMC/siRNA-s-s-PEG polyelectrolyte complexes were efficiently taken up by cancer cells upon exposure to a magnet, thereby enhancing intracellular uptake of siRNA. Furthermore, the PPMC/siRNA-s-s-PEG complexes in combination with an external magnetic field exhibited excellent silencing of target protein expression in cancer cells without showing severe cytotoxicity. The present study suggested that these novel nanomaterials could be potentially utilized for magnetically triggered delivery of various nucleic acid-based therapeutic agents. One of the important trends for biomedical technology is the “fusion” of different modalities to attain multifunctionality and highly accurate information on the system that we investigate. As a successful example of multimodality, we demonstrate magnetic nanoparticles to be used as a highly attractive platform for siRNA delivery in gene therapy as well as for imaging characteristics such as MRI and optics when conjugated to fluorescent dye. Also, this nanoparticle is harnessed to have specific cell targeting moieties on its surface in order to specifically target the integrin expressing cancer cells only. All of these modalities make the nanoparticle to have “all-in-one” capability which enables multimodal targeted imaging and siRNA gene therapy for the cancer c...