Synthetic molecules and functionalized nanoparticles targeting the LPS-TLR4 signaling: a new generation of immunotherapeutics

Toll-like receptor 4 (TLR4), the receptor of bacterial endotoxins in mammalians, plays a pivotal role in the induction of innate immunity and inflammation. TLR4 activation by bacterial lipopolysaccharide (LPS) is achieved by the coordinate and sequential action of three other proteins, LBP, CD14 and MD-2 receptors, that bind lipopolysaccharide (LPS) and present it in a monomeric form to TLR4 by forming the activated (TLR4-MD-2-LPS)2 complex. Small molecules and nanoparticles active in modulating the TLR4 signal by targeting directly the MD-2.TLR4 complex or by interfering in other points of the TLR4 signaling are presented in this paper. These compounds have great pharmacological interest as vaccine adjuvants, immunotherapeutics, anti-sepsis and anti-inflammatory agents