Leukocyte-Hitchhiking Nanomedicine for Sensitized Ferroptosis Therapy.

Effective drug aggregation at tumor sites is crucial for improving outcomes in triple-negative breast cancer. However, multiple biological barriers within the tumor microenvironment limit the clinical utility, efficacy, and safety of current therapeutics, leading to treatment failure and cancer recurrence. In this study, we develop an in vivo strategy to construct a cell-mediated nanomedicine in which E-selectin-modified liposomes are intravenously injected and selectively adhere to leukocyte surfaces. These leukocytes then transport the liposome aggregates to tumor sites via inflammatory tropism, significantly enhancing tumor accumulation and improving the recognition and treatment of metastasis. Moreover, the synergistic effect of the ferroptosis inducer RSL3 and nanozyme AuNPs coencapsulated in liposomes disrupts the cellular nutrient supply and damages the redox homeostasis under laser irradiation, which effectively suppresses tumor growth and lung metastasis through starvation therapy-amplified ferroptosis. These findings highlight the potential of the leukocyte-hitchhiking strategy for targeted drug delivery and demonstrate the broader applicability of cell-mediated nanomedicine in cancer treatment.