An sp2 Carbon-Conjugated Covalent Organic Framework for Fusing Lipid Droplets and Engineered Macrophage Therapy

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 sp2C-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 sp2C-conjugated COFs for engineered immune cell therapy, providing a new perspective for the development of therapeutic immune cells via organelle manipulation.