Acidic tumor cell lipid bilayer

The acidic tumor cell lipid bilayer is a distinct physiological target characterized by the low extracellular pH (pHe) environment surrounding cancer cells, typically ranging from 6.5 to 6.8 (Gatenby & Gillies, 2004, Nat Rev Cancer). This acidity is primarily a result of the Warburg effect, where cancer cells rely on anaerobic glycolysis and subsequent lactic acid secretion even in the presence of oxygen. This pH gradient between the acidic tumor microenvironment and the neutral systemic circulation (pH 7.4) allows for the development of pH-responsive therapeutic agents. These agents, such as pH-Low Insertion Peptides (pHLIPs) or pH-sensitive liposomes, undergo structural transitions or protonation in acidic conditions, enabling them to specifically insert into or fuse with the tumor cell membrane (Reshetnyak et al., 2008, PNAS). By targeting the lipid bilayer in this specific context, researchers can achieve selective delivery of imaging agents or toxins directly to malignant cells while sparing healthy tissues (Wyatt et al., 2017, Trends Biotechnol). This approach bypasses the need for specific protein receptors, which are often heterogeneously expressed in tumors, though it faces challenges regarding off-target effects in other naturally acidic tissues like the kidneys (Anderson et al., 2016, Mol Pharm).

Other names

Acidic tumor microenvironment membranepH-sensitive tumor membraneTumor cell lipid bilayerAcidic TME lipid bilayer

pH-dependent membrane insertion or destabilization, where the acidic extracellular environment triggers a conformational change in the drug or carrier, allowing it to penetrate or fuse with the lipid bilayer to deliver therapeutic cargo (Reshetnyak et al., 2008, PNAS).