Double-responsive platinum nanoclusters combined with CXCR4 antagonists and PD-L1 inhibitors for multimodal synergistic treatment of acute myeloid leukemia

Abstract Patients diagnosed with acute myeloid leukemia (AML) continue to encounter adverse outcomes, such as relapse, drug resistance, and toxicities, even after receiving treatment. Long-term AML control needs to explore a variety of novel treatment options because the core clinical treatment of AML has remained basically unchanged for the last few decades. The CXCR4/CXCL12 biological axis and the PD-1/PD-L1 immune checkpoint are regarded as potential targets for tumor treatment. The dual-responsive platinum nanoclusters are rationally designed for the treatment of AML, utilizing the CXCR4 antagonists and PD-L1 inhibitors, in conjunction with chemodynamic therapy. The findings indicate that platinum nanoclusters possess the capability to migrate into the bone marrow cavity of leukemic mice, inhibit AML cells from homing to the bone marrow or infiltrating into the liver and spleen, significantly enhance the anti-leukemia immune response, alleviate drug resistance, prolong the survival time of leukemic mice, and inhibit the growth and recurrence of leukemic mice. Hence, this multi-mechanism synergistic treatment strategy is anticipated to effectively address the recurrence and drug resistance of AML, thereby presenting an innovative approach for leukemia treatment.