Targeted modulation of macrophage functionality by nanotheranostics in inflammatory liver disease and cancer

Liver diseases characteristically progress from chronic inflammation to aberrant wound-healing with excessive scarring, termed fibrosis, and eventually to liver cancer. Since hepatic macrophages are critical regulators of these inflammatory processes, it appears promising to target these cells with novel nanomedicinebased therapeutics. Nanomedicine bears a large potential for the design of novel drugs by site-specific delivery and controlled release. Nanotheranostics allow for additional in vivo tracing of the therapeutics. Therapeutic nanoparticles are, in most cases, composed of biodegradable compounds such as phospholipids, which are an essential part of biological membranes. Nanodrugs may interact with soluble parts of the immune system (humoral immunity), specifically with components that help immune cells in pathogen recognition such as antibodies or complement factors. Macrophages are a heterogeneous cell type being composed of pro- or antiinflammatory subtypes that can either heal or worsen inflammatory diseases as well as combat or support cancer growth. Due to their inherent capability of foreign material uptake, macrophages are relatively easy to target, but may also hinder particles from reaching other target cells. A variety of receptors attractive for targeting was found to be useful in more specific strategies for selectively modulating macrophages to overcome effects on other cell types. In this chapter, current strategies to target macrophages in liver diseases and cancer are reviewed.