Harnessing CSC recruitment: photo-triggered “self-exploding” macrophages for targeted metastasis inhibition

Cancer metastasis is a serious threat to human health. Cancer stem cells (CSC) are closely related to tumor metastasis, but it is difficult to achieve accurate drug delivery and effective inhibition of CSC due to the complex tumor microenvironment. Herein, we report a living cell delivery system, C-H@M2, engineered by loading M2 macrophages with carrier-free Ce6/Honokiol self-assembled nanoparticles. This system is designed to harness the tumor’s intrinsic recruitment mechanism for targeted anti-metastasis therapy. Acting as a “Trojan Horse”, C-H@M2 exploits the active recruitment of M2 macrophages by CSC to achieve precise tumor homing. Upon laser irradiation, the macrophages undergo photo-triggered immunogenic lysis (“self-explosion”), leading to the burst release of therapeutic payloads and the induction of robust immunogenic cell death (ICD). HK as an inhibitor of Forkhead box M1 (FOXM1) inhibits CSC stemness and epithelial mesenchymal transition (EMT) in tumor tissues. In vivo experimental results demonstrate that C-H@M2 significantly inhibits tumor and lung metastasis through a triple-modal strategy: Self-explosion enhanced ICD effect, stemness and EMT inhibition, CSC killing by stemness inhibition and PDT. Our study provides a novel strategy for CSC targeted therapy and cancer metastasis inhibition.