Biomimetic lipid nanocarriers overcome hypoxia barriers in lung cancer therapy

Lung cancer, a major cause of cancer-related deaths, poses significant therapeutic challenges due to tumor hypoxia. Various drug delivery systems are designed to alleviate tumor hypoxia. However, their effectiveness is limited by complex physiological barriers, as well as issues like biocompatibility and colloidal stability. Natural lipids play key roles in physiological processes, including cellular interactions and immunomodulation, and are highly biocompatible. Herein, following the biomimetic concept of lung cancer cell membranes and the modulation of natural lipid nanostructures, we custom-designed lung cancer cell membrane-mimicking nanocarriers (LCCMNs) for efficient oxygen-generating drug delivery to hypoxic regions of lung tumors. The optimized nanocarriers effectively overcame various physiological barriers and possessed good biocompatibility and structural stability, thereby ensuring efficient drug delivery. Meanwhile, these nanocarriers, which carried lung cancer-associated glycolipid antigens and immune adjuvants, were more effective at alleviating the immunosuppression caused by hypoxia. As a proof-of-concept, we developed a self‑oxygenating nanosystem based on LCCMNs to enhance the efficacy of lung cancer treatment combining radiotherapy and immunotherapy, and this nanosystem efficiently improved therapeutic outcomes. Our development of LCCMNs aims to address the problem of hypoxia in lung tumors during treatment.