Erythrocyte-Based Biomimetic MOFs as a Triple Epigenetic Regulator for Enhancing Anti-Leukemia Immunity.

Nano Lett

State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun, 130012, China.

Published: December 2024

While therapeutic strategies targeting epigenetic dysregulation hold promise for leukemia, epigenetic drugs face several limitations, including low utilization rates, the emergence of resistance, and off-target effects. The hypoxic microenvironment in leukemia further impairs drug sensitivity. Here, we synthesized an MOF-based erythrocyte biomimetic nanoplatform to enhance immune responses against leukemia by targeting three epigenetic modifications. UiO-66-NH was loaded with two epigenetic drugs, along with oxygen-rich erythrocytes (red blood cells, RBCs). MA272@MOF@RBC suppressed hypoxia-induced factor (HIF-1α) and its downstream oncogenes, thereby enhancing the efficacy of the epigenetic drugs. The drugs inhibited the growth of leukemia cells by targeting DNA and histone methylation while enhancing mA-RNA methylation. MA272@MOF@RBC activated cytotoxic and memory T cells by increasing the antigenicity of leukemia cells. MA272@MOF@RBC also demonstrated immunotherapeutic effects on solid tumors. This was the first study to report the synthesis of triple epigenetic regulatory biomimetic MOFs with significant clinical potential for tumor immunotherapy.

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Source
http://dx.doi.org/10.1021/acs.nanolett.4c04264DOI Listing

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