Negatively charged tumor endothelial cell membrane

The negatively charged tumor endothelial cell membrane is a distinctive physiological feature of the tumor microenvironment, characterized by the abnormal exposure of anionic phospholipids, particularly phosphatidylserine (PS), on the outer leaflet of the plasma membrane (Ran et al., 2002). In normal vascular endothelium, these negatively charged lipids are sequestered in the inner leaflet, but oxidative stress and inflammatory cytokines in the tumor milieu trigger their externalization (Thorpe, 2004). This creates a selective target for cationic therapeutic agents, such as cationic liposomes (e.g., EndoTAG-1) and peptides, which bind via electrostatic interactions (Schmitt-Sody et al., 2003). Additionally, monoclonal antibodies like bavituximab have been developed to target these exposed phospholipids to induce vascular collapse and immune-mediated destruction of the tumor blood supply (Gerber et al., 2011). Targeting this membrane property offers a strategy to disrupt tumor angiogenesis and improve the delivery of cytotoxic drugs while sparing healthy tissues.

Other names

Anionic tumor vascular endotheliumPhosphatidylserine-exposed tumor endotheliumNegatively charged tumor vasculature

Electrostatic targeting of anionic phospholipids and antibody-mediated vascular disruption