Biomimetic Shell–Core Nanoparticles Loaded With Apatinib for Dual Starvation and Chemodynamic Combination Therapy of Lung Cancer

Tumor cells rely heavily on vascular nutrient supply and glucose metabolism to sustain proliferation, while maintaining redox homeostasis through reprogrammed antioxidant systems, making it difficult for single starvation therapy or chemodynamic therapy (CDT) alone to achieve durable and effective antitumor efficacy. To address these limitations, we developed a cancer cell membrane (CMC)‐coated core–shell biomimetic nanoplatform, termed ACuA@CMC, for synergistically enhanced dual‐starvation therapy and CDT. The nanoplatform consisted of a gold nanoparticle (Au NPs) core and a Cu 2 O shell. The Au NPs exhibited glucose oxidase‐like (GOx‐like) activity, enabling continuous glucose depletion and in situ H 2 O 2 generation within tumor cells, while the Cu 2 O shell further catalyzed H 2 O 2 into highly reactive ·OH under the tumor microenvironment, thereby amplifying oxidative stress. Meanwhile, the loaded apatinib (Apa) inhibited tumor angiogenesis and nutrient supply, which synergized with Au NPs‐mediated glucose consumption to establish a dual‐starvation therapeutic strategy. In addition, CMC coating endowed ACuA@CMC with favorable homologous targeting ability and enhanced cellular uptake efficiency. Experimental results demonstrated that ACuA@CMC possessed favorable physicochemical properties, stability, and hemocompatibility. Moreover, ACuA@CMC significantly enhanced the uptake of nanodrugs by A549 cells, effectively inhibited cell viability, induced apoptosis, elevated intracellular ROS levels, and triggered oxidative stress. Furthermore, the nanoplatform markedly suppressed tumor cell migration and downregulated VEGF expression, exhibiting synergistic anti‐migration and anti‐angiogenic effects. In summary, this study proposes a synergistic therapeutic strategy for lung cancer based on dual‐starvation therapy and cascade CDT‐mediated ROS amplification. This work provides a new approach for the development of multifunctional synergistic antitumor nanotherapeutic systems with potential clinical translational value.