Heme Oxygenase 1-targeted Drug Delivery Systems for Acute Myeloid Leukemia Therapy
발표자
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초록
내용
Acute myeloid leukemia (AML) is hematological malignancies with high mortality, and chemotherapy and bone marrow transplantation are available, and recently challenged with immunotherapy. Heme oxygenase 1 (HO1)-mediated cytoprotection has been demonstrated as a chemo-resistant mechanism in AML, and recently reported as an immune checkpoint molecule in tumor myeloid cell. In here, HO1-targeted drug delivery systems are developed for AML therapy. Firstly, human CD64-targeted single chain antibody fusion protein sR9 was complexed with HO1-targeting siRNA (siHO1). In human AML-bearing orthotopic model, sR9-mediated siHO1 delivery enhances chemotherapeutic effect of daunorubicin. Secondly, HO1-inhibitor-loaded nanoparticle (T-hNP) was prepared and modified for active targeting of AML. In human AML xenograft model, combination of T-hNP with daunorubicin shows dual chemo- and immuno-therapeutic effect.