final data for SECRIS effect.7z

Current strategy in developing secretory phospholipase A2 (sPLA2)-responsive liposomes merely considering substrate preference suffers from limited membrane disruptive effects induced by enzymatic hydrolysis and safety issues resulted from overuse of sPLA2–preferred lipids. Here, a state-of-the-art membrane-destabilzing mechanism captilizing on enzymatic extraction and transition of facial amphiphile (FA) within lipid membranes was introduced. Enzymatic degradation of FA-modified lipids, a process invovling substrate extraction of lipids out of membranes and cleavage of <em>sn-2</em> ester bonds by sPLA2, rotation and interface settling of detached FAs, caused tremendous efflux of payloads from liposomes, coined as SECRIS effect. Liposomes endowed with such effect showed enhanced drug release，excellent anti-tumor efficacy and reduced adverse syndromes when delivering oxaliplatin (L-OHP). Our discovery demonstrates a brand-new way in design of enzyme-liable nano-vesicles by fully exploiting special motion of substrates and their metabolites.