Amentoflavone-loaded nanoparticles enhanced chemotherapy efficacy by inhibition of AKR1B10

Therapeutic nanoparticles can be combined with different anticancer drugs to achieve a synergistic therapy and avoid the limitations of traditional medicine and thus have clinical prospects for cancer. Herein, an effective nanoplatform was developed for self-assembling AMF@DOX-Fe³⁺-PEG nanoparticles (ADPF NPs) via the coordination of ferric ions (Fe³⁺), amentoflavone (AMF), doxorubicin (DOX), and PEG-polyphenol. The ADPF NPs possessed high drug loading efficiency, good stability and dispersion in water, prolonged blood circulation, and pH-dependent release, which leading to targeted drug transport and enhanced drug accumulation in the tumor. The AMF from the ADPF NPs could inhibit the expression of the Aldo-keto reductase family 1B10 (AKR1B10) and nuclear factor-kappa B p65 (NF-κB p65), which reduced the cardiotoxicity induced by DOX and enhanced the chemotherapy efficacy. This study established a new strategy of combining drug therapy with a nanoplatform. This new strategy has a wide application prospect in clinical tumor therapy.