Fe3O4@Pt nanozymes combining with CXCR4 antagonists to synergistically treat acute myeloid leukemia

Abstract

Abstract Recurrence and drug resistance of acute myeloid leukemia (AML) remained the leading causes of death in blood cancers. The interaction of chemokine receptor 4/chemokine ligand 12 (CXCR4/CXCL12) leads to the trace residue of AML cells in patients after traditional chemotherapy, which hidden security danger for subsequent recurrence. The toxic and side effects of conventional chemotherapy on normal tissues also severely limited the clinical therapeutic efficacy of AML. To overcome these problems, a multifunctional nanoplatform of Fe3O4@Pt composite nanozyme conjugating CXCR4 antagonist was designed, aiming to synergistically treat AML for the first time, in which, the CXCR4 antagonist was used to specifically target AML cells as well as to significantly interfere CXCR4/CXCL12 axis. In the mildly acidic lysosome microenvironment, highly toxic reactive oxygen species (ROS) was generated through the sequential catalytic reactions of Fe3O4@Pt to trigger AML cells apoptosis, leaving the normal cells unharmed. This nanoplatform exhibited a superior synergistic therapeutic efficacy against AML in vitro and in vivo, preventing AML cells from homing to bone marrow and migrating to spleen, lung and liver, which in turn prolonged the survival period of AML mice. Therefore, this designed nanoplatform holds potentials for clinic applications in AML treatment.