Tang Chuanye, Feng Lei, Ling Pinghua, Wang Qiuting, Xu Wenwen, Song Danjie, Qiao Yalong, Gao Feng
Anhui Province Key Laboratory of Biomedical Materials and Chemical Measurement, College of Chemistry and Materials Science, Anhui Normal University, Wuhu 241002, China.
ACS Appl Mater Interfaces. 2025 Feb 19;17(7):10446-10456. doi: 10.1021/acsami.4c20737. Epub 2025 Feb 5.
Accurately and sensitively identifying and killing cancer cells, especially those in deep tissues, is of paramount importance but presents significant challenges. Herein, a membrane protein and adenosine triphosphate (ATP)-driven DNA logic gate-modified liposome is designed to coat zinc peroxide (ZP) nanoparticles integrated with nanozymes (ZP/RuTe@L/DNA) to accurately identify and induce cell apoptosis in cancer cells through a reactive oxygen species (ROS)-mediated mechanism under acid conditions in cancer cells. In this system, DNA logic gate-functionalized liposomes are loaded with ZP and nanozymes, while HeLa cancer cells are functionalized with a DNA segment that is complementary to a segment of the DNA logic gate. For the DNA logic gate, a DNA aptamer was employed for membrane protein recognition, and another aptamer was used for the response of extracellular ATP. Activation of the DNA logic gate occurs only when both biomarkers are simultaneously present. Once activated, the DNA logic gate-modified liposome could hybridize with DNA segment-modified HeLa cells, leading to liposome-HeLa cell fusion and the release of ZP/RuTe into HeLa cells. Under acid conditions, ZP could decompose to release HO and Zn, which could promote the production of •O and HO by inhibiting the electron transport chain. Concurrently, the released RuTe exhibits glutathione (GSH) depletion and peroxidase (POD) and nicotinamide adenine dinucleotide (NADH) peroxidase-like activities, generating highly toxic hydroxyl radical (•OH), disrupting the cellular redox homeostasis, and inducing cell apoptosis. The ZP/RuTe@L/DNA system could not only accurately detect cancer cells in complex cell mixtures but also present a novel method for liposome-membrane fusion processes in drug delivery. This study presents significant potential for application in precise cancer diagnosis and therapy.
准确且灵敏地识别并杀死癌细胞，尤其是深层组织中的癌细胞，至关重要但也面临重大挑战。在此，设计了一种膜蛋白和三磷酸腺苷（ATP）驱动的DNA逻辑门修饰脂质体，用于包裹与纳米酶整合的过氧化锌（ZP）纳米颗粒（ZP/RuTe@L/DNA），以在癌细胞酸性条件下通过活性氧（ROS）介导的机制准确识别并诱导癌细胞凋亡。在该系统中，DNA逻辑门功能化脂质体负载有ZP和纳米酶，而HeLa癌细胞则用与DNA逻辑门片段互补的DNA片段进行功能化。对于DNA逻辑门，使用DNA适配体进行膜蛋白识别，另一个适配体用于细胞外ATP的响应。只有当两种生物标志物同时存在时，DNA逻辑门才会被激活。一旦激活，DNA逻辑门修饰的脂质体就可以与DNA片段修饰的HeLa细胞杂交，导致脂质体 - HeLa细胞融合，并将ZP/RuTe释放到HeLa细胞中。在酸性条件下，ZP可以分解释放HO和Zn，这可以通过抑制电子传递链来促进•O和HO的产生。同时，释放的RuTe表现出谷胱甘肽（GSH）消耗以及过氧化物酶（POD）和烟酰胺腺嘌呤二核苷酸（NADH）过氧化物酶样活性，产生高毒性的羟基自由基（•OH），破坏细胞氧化还原稳态并诱导细胞凋亡。ZP/RuTe@L/DNA系统不仅可以在复杂细胞混合物中准确检测癌细胞，还为药物递送中的脂质体 - 膜融合过程提供了一种新方法。本研究在精确癌症诊断和治疗方面具有巨大的应用潜力。
