Biomimetic photodynamic nanoparticles exert anti-tumor therapy by inducing ferroptosis in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) has a high incidence and mortality. Conventional therapeutics suffer from poor targeting and severe side effects, making it still a great challenge to provide safe and effective treatment strategies. Photodynamic therapy (PDT) is a treatment option that is minimally invasive to patients and can be used repeatedly, and it is widely applied in clinical practice. However, PDT alone is limited by insufficient efficacy, tumor hypoxia, short circulation time in vivo , and low targeted delivery efficiency. The nanodelivery system provides important support for combination therapy and efficient drug delivery. In this study, biomimetic self-oxygenating nanoparticles (M1@CAT-Ce6-Rh2 Lips) were constructed. Using 20(S)-Ginsenoside Rh2 (Rh2) as the membrane material, the system achieves stable co-loading of the chlorin e6 (Ce6) and catalase (CAT), and is surface-modified with an M1 macrophage membrane. In this system, ginsenoside Rh2 serves as a key anti-tumor component that targets SLC7A11, GPX4, and the ferroptosis pathway; it directly inhibits the SLC7A11/GSH/GPX4 antioxidant axis, reduces GSH synthesis and GPX4 activity, promotes iron overload and lipid peroxidation, and synergizes with PDT to induce ferroptosis, while stabilizing the liposomal membrane structure. CAT decomposed hydrogen peroxide (H 2 O 2 ) to relieve tumor hypoxia, and the M1 macrophage membrane coating enabled active targeting and prolonged circulation. The nanosystem triggered rapidly accumulates through reactive oxygen species (ROS) and reduces the levels of solute carrier family 7 member 11 (SLC7A11), glutathione (GSH) and glutathione peroxidase 4 (GPX4), triggering ferroptosis to exert its effect.thereby realizing synergistic antitumor activity between Rh2 and PDT, and effectively suppressing the progression of NSCLC. This strategy shows promising application prospects in tumor biomimetic nanotherapy.