Tumor Cell Membrane-Camouflaged Biomimetic Liposomes for Targeted Delivery of Phytosphingosine with Enhanced Anti-Lung Cancer Activity

Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for over 80% of cases. Conventional chemotherapy is severely limited by insufficient tumor targeting, severe off-target systemic toxicity, and poor bioavailability of hydrophobic antitumor agents, which greatly compromise therapeutic efficacy and patient quality of life. Phytosphingosine (PHS), a natural sphingolipid with potent antitumor activity via cell cycle regulation and apoptosis induction, is hindered by low water solubility and dose-dependent systemic toxicity, restricting its clinical translation. To address these critical obstacles, we fabricated a biomimetic liposomal nanosystem (PHS-LPs@CCM) by camouflaging PHS-loaded liposomes with homologous NCI-H1299 lung cancer cell membranes. The resulting nanoparticles exhibited favorable colloidal stability, uniform size distribution, and excellent hemocompatibility, with the membrane coating retaining native surface adhesion molecules for specific homotypic recognition. This bioinspired design markedly enhanced cellular internalization in NCI-H1299 cells compared with uncoated liposomes. In vitro functional studies demonstrated that PHS-LPs@CCM induced significant G0/G1 phase arrest and ROS-dependent mitochondrial apoptosis, while effectively suppressing cell migration and invasion by inhibiting the epithelial-mesenchymal transition (EMT) process. This biomimetic colloidal platform offers a promising strategy to improve the delivery, efficacy, and safety of hydrophobic antitumor drugs, providing valuable implications for the design of biointerfacial functional nanocarriers for targeted cancer therapy.