Aspherical, Nanostructured Microparticles for Targeted Gene Delivery to Alveolar Macrophages

Abstract

Introducing novel shapes to particulate carrier systems adds unique features to modern drug and gene delivery. Depending on the route of administration, particle geometry can influence deposition and fate within biological environments. In this work, a template-assisted engineering technique is applied, providing full control of size and shape in the preparation of aspherical, nanostructured microparticles. Based on the interconnection of nanoparticles, stabilized by a functional layer-by-layer (LbL) coating, the resulting cylindrical micrometer architecture is especially qualified for pulmonary delivery. Designed as gene delivery system, plasmid-DNA (pCMV-luciferase) and branched polyethylenimine are used to reach both structural integrity of the carrier system and delivery of genes into the cells of interest. Due to their size, particles are exclusively taken up by phagocytes, which also adds a targeting effect to the introduced system. The luciferase expression is demonstrated in macrophages showing increasing levels over a time period of at least 7 d. Furthermore, it is shown for the first time that the expression is depending on the LbL design. From in vivo experiments, corresponding luciferase expression is observed in mice alveolar macrophages. Combining site specific transport with the possibility of genetically engineering immunocompetent phagocytes, the presented system offers promising potential to improve applications for cell-based immunotherapy.