SOD-like activity of CeO
2
nanoparticles (Ce NPs) is driven by Ce
3+
/Ce
4+
, high oxidative stress can oxidize Ce
3+
to reduce the ratio of Ce
3+
/Ce
4+
, inactivating the SOD activity of Ce NPs. Herein, we found Au@Ce NPs, assembled by Au NPs and Ce NPs, exhibited high-performance of SOD mimetic enzyme activity even upon the oxidation of H
2
O
2
. Ce NPs supported by nano-Au can acquire the electrons from Au NPs through the enhanced localized surface plasmon resonance (LSPR), maintaining the stability of Ce
3+
/Ce
4+
and SOD-like activity. Meanwhile, Au@Ce NPs retained the peroxidase function and catalase function. As a result, Au@Ce NPs effectively scavenged O
2
•- and the derived ROS in AML cells, which are the important signaling source that drives AML cell proliferation and accelerates cell cycle progression. When HL-60 cells were treated by Au@Ce NPs, the removal of endogenous ROS signal significantly arrested cell cycle at G1 phase and suppressed the cell proliferation by blocking the mitogen-activated protein kinases (MAPKs) signaling and the Akt/Cyclin D1 cell cycle signaling. Importantly, this treatment strategy showed therapeutic effect for subcutaneous transplantation of AML model as well as a satisfactory result in diminishing the leukocyte infiltration of liver and spleen particularly. Thus, assembled Au@Ce NPs show the high-performance SOD-like activity, promising the potential in treating AML and regulating abnormal ROS in other diseases safely and efficiently.
Guanfu base A·HCl (GFA·HCl) solution, approved by the China Food and Drug Administration (CFDA) in 2005, has been used in the treatment of arrhythmia. However, the poor targeting and absorption of GFA·HCl have severely affected its clinical application. In this study, a nanolipid-based, Guanfu base A (GFA) delivery system was designed to improve the deficiency of GFA·HCl and realize better clinical effect. The GFA-loaded solid nanolipids (GFASN) with a core/shell structure, composed of Poloxamer 188, lecithin, and medium-chain fatty acid, were prepared using a high-pressure homogenate emulsification method. Results showed that GFASN possessed well morphology and stability during the process of lyophilization and rehydration at 220-260 nm. Safety evaluation revealed that ear vein injection of GFASN (14 mg/kg) were safe enough and of good biocompatibility. More importantly, GFASN can better alleviate the arrhythmia of rats, especially in ventricular ectopia and ventricular tachycardia, than GFA·HCl solution. Pharmacokinetic behaviors and targeting evaluation in mice demonstrated that nanolipids can help GFA achieve longer circulation time in blood and better heart specificity. Collectively, these promising findings suggested that this kind of nanolipids was an ideal delivery carrier for GFA in the treatment of cardiovascular disease.
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