Red blood cell membrane-coated FLT3 inhibitor nanoparticles to enhance FLT3-ITD acute myeloid leukemia treatment

FMS-like tyrosine kinase 3(FLT3)is a viable and important therapeutic target for acute myeloid leukemia(AML).FLT3 internal tandem duplication(FLT3-ITD)mutations have been identified in approximately 30%of AML patients,and are associated with unfavorable prognosis,higher risk of relapse,drug resistance,and poor clinical outcome.Even FLT3 inhibitors have demonstrated promising efficacy,they cannot cure AML or even significantly extend the lives of patients with FLT3-ITD mutations.This is partly because of poor water solubility,insufficient membrane penetration and short half-life of small molecule inhibitors.Besides,the presence of enzymes like CYP3A4 in bone marrow accelerate the elimination and metabolism of FLT3 inhibitors,resulting in low plasma concentrations and side effects.Here we report the erythrocyte membrane-camouflaged FLT3 inhibitor nanoparticles to enhance FLT3-ITD AML treatment.Briefly,we physically coextruded red blood cell(RBC)membrane vesicles with nanoparticles derived from FLT3 inhibitor F30 to obtain F30@RBC-M,which exhibited comparable potent FLT3-ITD inhibitory effects compared to free F30 in vitro,while displaying a higher potent antitumor efficacy in xenograft models due to the prolonged circulation properties.Furthermore,administration of F30@RBC-M significantly extended the survival of mice in a transplanted mouse model than F30 free drug.These findings suggest that RBC membrane-coated nanoparticles derived from FLT3 inhibitors hold promise as a tool to enhance the therapeutic efficacy to treat FLT3-ITD AML.

FeCo alloy/N,S co-doped carbon aerogel derived from directionalcasting cellulose nanofibers for rechargeable liquid flow and flexible Zn–air batteries

Bifunctional oxygen reduction reaction(ORR)and oxygen evolution reaction(OER)electrocatalysts with the advantages of excellent activity and stability are the vital components of air cathodes for rechargeable Zn–air batteries(ZABs).Herein,the carbon aerogel with honeycomb-like structure,N and S double doping and loaded with FeCo alloy nanoparticles(NSCA/FeCo)was prepared successfully as cathodes for rechargeable liquid flow and two-dimensional flexible ZABs by clever directional casting.The interaction between the bimetallic alloy and the double-doped carbon with specifical structure,large surface,great conductivity endows NSCA/FeCo with effective ORR/OER active sites and small charge/mass transport barrier,thus achieving outstanding bifunctional catalytic performance.The NSCA/FeCo displays a half-wave potential of+0.85 V(vs.reversible hydrogen electrode(RHE))for ORR and an overpotential of 335 mV at a current density of 10 mA·cm^(−2)for OER,which is even comparable to the performance of noble-metal catalysts in relevant fields(Pt/C for ORR and RuO_(2)for OER).Consequently,the rechargeable liquid flow ZABs assembled with NSCA/FeCo showed excellent performance(maximum power density:132.0 mW·cm^(−2),specific capacity:804.5 Wh·kg^(−1)at 10 mA·cm^(−2),charge and discharge cycle stability of more than 250 cycles).Furthermore,the flexible NSCA/FeCo-based ZABs have a maximum power density of 43.0 mW·cm^(−2),outstanding charging–discharge stability of more than 450 cycles,exhibit good flexibility under different bending conditions.Therefore,this work has provided an efficient bifunctional electrocatalyst for OER/ORR and a promising strategy of air cathodes for rechargeable and wearable ZABs.