Tumor cell membrane camouflaged liposomal pharmaceuticals for cascade catalysis-driven redox modulation and synergistic ROS/RNS antitumor therapy

The antioxidant defense system (ADS) within the tumor microenvironment restricts the efficacy of reactive oxygen species (ROS) based therapies by conferring intrinsic redox tolerance. To overcome this limitation, we develop a tumor cell membrane camouflaged liposomal nanoplatform (C-MLip@LA) that modulates the ADS to enhance tumor-targeted therapy through a synergistic reactive oxygen/nitrogen species (ROS/RNS) cascade. The system encapsulates L-arginine (LA) as the core, anchors MnO 2 nanoparticles on the liposomal surface, and is cloaked with homologous tumor cell membranes, thereby enabling tumor-specific recognition and immune evasion. C-MLip@LA disassembles after cellular internalization, where MnO 2 depletes intracellular glutathione (GSH) and is reduced to Mn 2 + , thereby elevating ROS levels and enabling T 1 -weighted magnetic resonance imaging. Concurrently, the released LA reacts with endogenous H 2 O 2 to generate nitric oxide (NO). The interplay between NO and ROS initiates a cascade reaction that produces highly cytotoxic peroxynitrite, thereby amplifying immunogenic cell death and leading to pronounced tumor growth inhibition in a CT-2A tumor model. Collectively, this work presents a biomimetic nanoplatform for redox-modulated cancer therapy with integrated diagnostic and immunomodulatory functions.