Aspherical, Nanostructured Microparticles for Targeted Gene Delivery to Alveolar Macrophages. Issue 20 (20th July 2017)

• Record Type: Journal Article
• Authors: Möhwald, Michael; Pinnapireddy, Shashank Reddy; Wonnenberg, Bodo; Pourasghar, Marcel; Jurisic, Marijas; Jung, Andrea; Fink‐Straube, Claudia; Tschernig, Thomas; Bakowsky, Udo; Schneider, Marc
• Is Part Of: Advanced healthcare materials. Volume 6:Issue 20(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-07-20
• Subjects: aspherical particles -- layer‐by‐layer -- macrophage transfection -- mouse lung models -- pulmonary application; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.201700478
• Languages: English
• ISSNs: 2192-2640

Abstract

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. Abstract : A novel aspherical, nanostructured microparticle for pulmonary gene delivery is fabricated utilizing a template‐assisted engineering technique. Here, nanoparticles build up rod‐like shaped structures in the micrometer size range, stabilized with plasmid‐DNA and polyethylenimine. The carrier provides the introduction of genes into alveolar macrophages both in vitro and in vivo, qualifying the system for the genetic engineering of immunocompetent phagocytes.