Macrophage-Based Nanoplatforms for Tumor-Targeted Drug Delivery and Cancer Immunomodulation: Extracellular Vesicles, Membrane-Coated Nanoparticles, and Live Cells.

Macrophages are highly plastic immune cells with tumor-homing capacity and immunomodulatory functions, making macrophage-based nanoplatforms attractive for cancer immunotherapy. Macrophage-based nanoplatforms include macrophage-derived extracellular vesicles (EVs), macrophage membrane-coated nanoparticles, and live macrophage carriers. The platforms combine the biological properties of macrophages with the advantages offered by nanocarriers to achieve targeted delivery and immune regulation. Beyond serving as delivery vehicles, macrophages can be therapeutically reprogrammed through strategies such as CD47-SIRPα blockade and TLR7/MyD88 pathway activation to enhance antitumor immunity. Despite promising preclinical outcomes, clinical translation of macrophage-based Biomimetic nano-drug delivery systems (BNDDS) remains challenging due to cytokine release syndrome risk, scalable manufacturing limitations, and species differences between animal models and human immunity. The review provides insights into the development and clinical translation of macrophage-based BNDDS for cancer therapy.