An sp 2 Carbon‐Conjugated Covalent Organic Framework for Fusing Lipid Droplets and Engineered Macrophage Therapy

Abstract Engineered immune cell therapy has proven to be a transformative cancer treatment despite the challenges of its prohibitive costs and manufacturing complexity. In this study, we propose a concise “lipid droplet fusion” strategy for engineering macrophages. Because of the integration of hydrophobic alkyl chains and π‐conjugated structures, the mildly synthesized sp 2 C‐conjugated covalent organic framework (COF) UM‐101 induced lipid droplet fusion and metabolic reprogramming of macrophages, thus promoting their antitumor classical activation. Intravenous injection of UM‐101 –engineered macrophages effectively inhibited tumor progression. These results represent the first report of room‐temperature synthesis of sp 2 C‐conjugated COFs for engineered immune cell therapy, providing a new perspective for the development of therapeutic immune cells via organelle manipulation.