肿瘤中分泌性磷脂酶 A2 (sPLA2) 的上调已被提议作为触发药物从脂质体中释放以达到治疗效果的刺激物。然而，目前仅考虑底物偏好来开发 sPLA2 响应脂质体的策略受到酶水解诱导的有限膜破坏作用以及由于过度使用 sPLA2 偏好脂质而导致的安全问题的影响。在这里，介绍了一种基于酶提取和脂膜内表面两亲物（FA）转变的膜不稳定机制。 FA 修饰脂质的酶促降解过程涉及从膜中提取脂质的底物以及 sPLA2 裂解 sn-2 酯键、旋转以及分离 FA 的界面沉降，导致有效负载从脂质体中大量流出，称为 SECRIS 效应。在 sPLA2 存在的情况下，与传统 sPLA2 不稳定的小鼠相比，含有 FA 修饰脂质的奥沙利铂 (L-OHP) 负载脂质体显示出增强的药物释放、相当的体外细胞毒性和优异的体内抗肿瘤功效，并减少了 Colo205 小鼠的不良症状配方。 SECRIS 效应的发现为设计用于治疗 sPLA2 阳性肿瘤的脂质体平台开辟了一条新途径。

Upregulated secretory phospholipase A2 (sPLA2) in tumors has been proposed as a stimulus to trigger drug release from liposomes for therapeutic effects. However, the current strategy for developing sPLA2-responsive liposomes merely considering substrate preference suffers from limited membrane disruptive effects induced by enzymatic hydrolysis and safety issues resulting from the overuse of sPLA2-preferred lipids. Here, a membrane-destabilizing mechanism based on enzymatic extraction and the transition of facial amphiphiles (FAs) within lipid membranes was introduced. Enzymatic degradation of FA-modified lipids, a process involving substrate extraction of lipids from membranes and cleavage of sn-2 ester bonds by sPLA2, rotation, and interface settling of detached FAs, caused tremendous efflux of payloads from liposomes, termed the SECRIS effect. In the presence of sPLA2, oxaliplatin (L-OHP) loaded liposomes containing FA-modified lipids showed enhanced drug release, comparable in vitro cytotoxicity, and excellent in vivo antitumor efficacy and reduced adverse syndromes in Colo205-bearing mice compared to conventional sPLA2-labile formulations. The discovery of the SECRIS effect creates a new pathway to engineer liposome platforms for the treatment of sPLA2-positive tumors.