Biomimetic platelet membrane-camouflaged liposomes with RBCs hitchhiking enable efficient targeting and suppression of lung metastasis

Activated platelet membranes upregulate tumor adhesion markers. • Liposomes with activated PLMs target CTCs efficiently. • RBC-hitchhiking technique enhances liposomal lung targeting and circulation. • The RBC-PLM-lipo system integrates biomimetic and physical targeting strategies. • A novel DDS shows promising efficacy against lung cancer CTCs and metastasis. Circulating tumor cells (CTCs) drive metastasis via bloodstream dissemination and are recognized as a leading cause of cancer-related mortality. Current targeting strategies using single surface receptors often suffer low efficiency and off-target toxicity. CTCs induce thrombosis to form a protective cloak against immune attack. Inspired by this, we used activated platelet membranes (PLMs), which show upregulated adhesion-related markers, to prepare pH-sensitive paclitaxel-loaded liposomes, offering superior tumor targeting. The RBC-hitchhiking technique further enhanced liposomal lung targeting and circulation time. Integrating these advantages, we developed an RBC-PLM-lipo drug delivery system (DDS) and evaluated it against lung cancer CTCs-induced metastases. Our results showed that RBC-PLM-lipo DDS targets lung cancer, inhibits tumor growth, reduces the M2/M1 macrophage ratio, and reverses the immune-suppressive microenvironment. Thus, this DDS improves conventional chemotherapy efficacy, reduces off-target toxicity, and maximizes clinical benefit for lung cancer patients.