CD71-mediated liposomal arsenic-nickel complex combined with all-trans retinoic acid for the efficacy of acute promyelocytic leukemia

Clinically,arsenic trioxide(ATO)was applied to the treatment of acute promyelocytic leukemia(APL)as a reliable and effective frontline drug.However,the administration regimen of AsⅢwas limited due to its fast clearance,short therapeutic window and toxicity as well.Based on CD71 overexpressed on APL cells,in present study,a transferrin(Tf)-modified liposome(LP)was established firstly to encapsulate AsⅢin arsenic-nickel complex by nickel acetate gradient method.The AsⅢ-loaded liposomes(AsLP)exhibited the feature of acid-sensitive release in vitro.Tf-modified AsLP(Tf-AsLP)were specifically taken up by APL cells and the acidic intracellular environment triggered liposome to release AsⅢwhich stimulated reactive oxygen species level and caspase-3 activity.Tf-AsLP prolonged half-life of AsⅢin blood circulation,lowered systemic toxicity,and promoted apoptosis and induced cell differentiation at lesion site in vivo.Considering that ATO combined with RA is usually applied as the first choice in clinic for APL treatment to improve the therapeutic effect,accordingly,a Tf-modified RA liposome(Tf-RALP)was designed to reduce the severe side effects of free RA and assist Tf-AsLP for better efficacy.As expected,the tumor inhibition rate of Tf-AsLP was improved significantly with the combination of Tf-RALP on subcutaneous tumor model.Furthermore,APL orthotopic NOD/SCID mice model was established by 60CO irradiation and HL-60 cells intravenously injection.The effect of co-administration(Tf-AsLP+Tf-RALP)was also confirmed to conspicuous decrease the number of leukemia cells in the circulatory system and prolong the survival time of APL mice by promoting the APL cells’apoptosis and differentiation in peripheral blood and bone marrow.Collectively,Tf-modified acid-sensitive AsLP could greatly reduce the systemic toxicity of free drug.Moreover,Tf-AsLP combined with Tf-RALP could achieve better efficacy.Thus,transferrinmodified AsⅢliposome would be a novel clinical strategy to improve patient compliance,with promising translation prospects.

Bioinspired nanofluidic iontronics for brain-like computing

The human brain performs computations via a highly interconnected network of neurons.Taking inspiration from the information delivery and processing mechanism of the human brain in central nervous systems,bioinspired nanofluidic iontronics has been proposed and gradually engineered to overcome the limitations of the conventional electron-based von Neumann architecture,which shows the promising potential to enable efficient brain-like computing.Anomalous and tunable nanofluidic ion transport behaviors and spatial confinement show promising controllability of charge carriers,and a wide range of structural and chemical modification paves new ways for realizing brain-like functions.Herein,a comprehensive framework of mechanisms and design strategy is summarized to enable the rational design of nanofluidic systems and facilitate the further development of bioinspired nanofluidic iontronics.This review provides recent advances and prospects of the bioinspired nanofluidic iontronics,including ion-based brain computing,comprehension of intrinsic mechanisms,design of artificial nanochannels,and the latest artificial neuromorphic functions devices.Furthermore,the challenges and opportunities of bioinspired nanofluidic iontronics in the pioneering and interdisciplinary research fields are proposed,including brain–computer interfaces and artificial neurons.