Magnetized Cellular Robots for Precision Cytokine Delivery: A Novel Approach to Tumor-Targeted Therapy

Cancer has become the second major health threat endangering human survival and represents a core challenge requiring urgent resolution in global public health. Immunotherapy is a novel therapeutic strategy that combats cancer by modulating the immune system. Although several immunotherapeutic agents have been clinically applied for cancer treatment, the presence of 'cold' tumors in some patients leads to low response rates to immunotherapy. Potential off-target effects and other adverse events remain significant challenges in tumor immunotherapy. In this study, to address the limitations of immunotherapy for lymphoma, a highly heterogeneous and aggressive cold tumor, we designed chemokine (C-C motif) ligand 5 (CCL5)-loaded macrophagebased microrobots to remodel the tumor microenvironment. This strategy synergistically integrates the inherent phagocytic functionality and tumor-tropic properties of macrophages with the biosafety advantages, tetherless operational capacity, and spatiotemporal precision of magnetically navigated platforms. CCL5 mediates immune cell chemotaxis and enhances tumor cell infiltration and metastatic potential. We conjugated cytokines to the surface of magnetic nanoparticles using the carbodiimide method, achieving excellent biocompatibility and magnetic responsiveness. The transwell assay confirmed the engineered macrophages' innate tumor tropism and magnetic field-guided targeting capability toward EL-4 cells. These magnetically responsive macrophages demonstrate potential for advancing safer and more effective clinical translation of immunotherapies. Our strategy facilitates immune cell reprogramming and recruitment, establishing a novel platform for tumor immunotherapy.