CeO2@CA@PEI@dextran improves drug sensitivity in chronic myelogenous Leukemia through scavenging free radical efficiently

The sustained free radicals derived from drug-resistant chronic myeloid leukemia (CML) cells can trigger oxidative stress, thereby reducing cell drug sensitivity and therapeutic efficacy. Our prior work demonstrated that dextran-modified ceria nanoparticles (CeO 2 NPs) exhibit the intrinsic antioxidant capability and are capable of enhancing anti-leukemia therapeutic responses. However, excessive intracellular free radicals trigger the interfacial electron transfer across nano-enzymatic surfaces, disrupting Ce 3+ /Ce 4+ valence equilibrium and compromising their long-term antioxidant performance. Here, we found that CeO 2 NPs modified by citric acid (CA) and polyethyleneimine (PEI) and dextran (CeO 2 @CA@PEI@Dextran) provided the long-lasting capacity to scavenge radicals by the aid of electronic buffer effect of CA@PEI, which can buffer the process of electronic gain and loss to maintain the stability of Ce 3+ /Ce 4+ ratio and a long-term performance to scavenge free radicals in vitro and in vivo. CeO 2 @CA@PEI@Dextran thus regulated intracellular oxidative stress persistently to improve the effects of doxorubicin in K562-ADR cells, one CML cell line resistant to doxorubicin. In contrast, the regulatory effect of small-molecule antioxidants such as N -acetylcysteine and glutathione in diminishing free radicals is unsustainable and undulant. Consequently, reshaping the redox homeostasis in CML patients by the continuous anti-oxidation mediated by CeO 2 @CA@PEI@Dextran may be a potential way to improve the treatment of drug-resistant patients, distinct from the unsustainable anti-oxidation strategies, which presents a novel perspective for clinical drug usage. Scheme 1 CeO 2 nanoparticles modified by citric acid (CA) and polyethyleneimine (PEI) and Dextran (CeO 2 @CA@PEI@Dextran) provided the long-lasting capacity to scavenge radicals by the aid of electronic buffer effect of CA@PEI, which can buffer the process of electronic gain and loss to maintain the stability of Ce 3+ /Ce 4+ ratio and a long-term performance to scavenge free radicals. CeO 2 @CA@PEI@Dextran thus regulated intracellular oxidative stress persistently to improve the drug sensitivity in drug-resistant CML cells. Download: Download high-res image (288KB) Download: Download full-size image