Enhanced macrophage delivery to the colon using magnetic lipoplexes with a magnetic field

Abstract

Magnetically guided cell delivery systems would be valuable to achieve effective macrophage-based cell therapy for colonic inflammatory diseases. In the current study, we developed a method for the efficient and simultaneous introduction of superparamagnetic iron oxide nanoparticles (SPIONs) and plasmid DNA (pDNA) into RAW264 murine macrophage-like cells using SPION-incorporated cationic liposome/pDNA complexes (magnetic lipoplexes). SPIONs and pDNA were introduced for magnetization and functionalization of the macrophages, respectively. We also evaluated the adhesive properties of magnetized RAW264 cells using magnetic lipoplexes in the murine colon under a magnetic field. Significant cellular association and gene expression without cytotoxicity were observed when magnetic cationic liposomes and pDNA were mixed at a weight ratio of 10:1, and SPION concentration and magnetic field exposure time was 0.1 mg/mL and 10 min, respectively. We also observed that cytokine production in magnetized RAW264 cells was similar to that in non-treated RAW264 cells, whereas nitric oxide production was significantly increased in magnetized RAW264 cells. Furthermore, magnetized RAW264 cells highly adhered to a Caco-2 cell monolayer and colon in mice, under a magnetic field. These results suggest that this magnetic cell delivery system can improve the colonic delivery of macrophages and its therapeutic efficacy against colonic inflammatory diseases.