Erythrocyte-Based\nBiomimetic MOFs as a Triple Epigenetic\nRegulator for Enhancing Anti-Leukemia Immunity

While therapeutic strategies targeting\nepigenetic dysregulation\nhold promise for leukemia, epigenetic drugs face several limitations,\nincluding low utilization rates, the emergence of resistance, and\noff-target effects. The hypoxic microenvironment in leukemia further\nimpairs drug sensitivity. Here, we synthesized an MOF-based erythrocyte\nbiomimetic nanoplatform to enhance immune responses against leukemia\nby targeting three epigenetic modifications. UiO-66-NH<sub>2</sub> was loaded with two epigenetic drugs, along with oxygen-rich erythrocytes\n(red blood cells, RBCs). MA272@MOF@RBC suppressed hypoxia-induced\nfactor (HIF-1α) and its downstream oncogenes, thereby enhancing\nthe efficacy of the epigenetic drugs. The drugs inhibited the growth\nof leukemia cells by targeting DNA and histone methylation while enhancing\nm<sup>6</sup>A-RNA methylation. MA272@MOF@RBC activated cytotoxic\nand memory T cells by increasing the antigenicity of leukemia cells.\nMA272@MOF@RBC also demonstrated immunotherapeutic effects on solid\ntumors. This was the first study to report the synthesis of triple\nepigenetic regulatory biomimetic MOFs with significant clinical potential\nfor tumor immunotherapy.