Neutrophil-Mediated Tumor Discrimination Biomimetic Nanodevice for Precise Tumor Eradication and Metastasis Cascade Perturbing

The deficient discrimination of tumor cells, limited accumulation of therapeutic agents in tumor foci, and undesirable tumor metastasis result in compromised therapeutic efficacy in antitumor therapy. Neutrophils, the most abundant circulating leukocytes, are key players in tumor progression and have a high affinity to tumors. Herein, a biomimetic tumor discrimination nanodevice (NL-FSB) is developed by harboring a pH-sensitive Fenton agent (FSB) in an activated neutrophil membrane-incorporated liposome for tumor-specific ablation. Inheriting the biointerfacing properties of neutrophils, NL-FSB is endowed with high affinity to tumors. On one hand, NL-FSB can be recruited to acidic tumor sites mediated by chemotaxis attraction and selectively generate reactive oxygen species via amplified Fenton chemical reaction for specific tumor eradication. On the other hand, the biomimetic NL-FSB can also target and bind tumor vascular endothelium or circulating tumor cells (CTCs) in circulation, executing pseudo escort to perturb CTC-neutrophil cluster formation and tumor metastasis cascade. Unprecedentedly, the neutrophil-mediated nanoagent can effectively inhibit the already-formed tumor and prevent tumor metastasis with high specificity. Our study represents a promising yet simple strategy for tumor-specific killing and metastasis cascade blockage via a nanobioengineering functionalization strategy.