Staggered herringbone micromixer has shown good efficiency of mixing and performance of synthesizing nanoparticles.To bring a detailed understanding of the mixing dynamics and syn-thesis performance of this kind of mi...Staggered herringbone micromixer has shown good efficiency of mixing and performance of synthesizing nanoparticles.To bring a detailed understanding of the mixing dynamics and syn-thesis performance of this kind of micromixer,this paper carries out a high-fidelity numerical simu-lation and a parametrial experimental study on a well-established design.A passive tracer is induced in the numerical simulation to analyze mixing dynamics induced by the staggered herring-bone structures.Three effects are identified to reveal the underlying mechanisms,including folding,stretching,and splitting.To the authors’knowledge,the splitting effect is identified for the first time by the isosurface of the passive tracer,to show the high efficiency of the staggered herring-bone design.The micromixer is then used to synthesize lipid nanoparticles by mixing a mixture of lipid and poly(lactic-co-glycolic acid)(PLGA)solutions with deionized water.Under a wide mass ratio of lipid and PLGA solutions,nanoparticles with good monodispersity are synthesized to reflect the good compatibility of the micromixer and the mixture.In addition,an optimized mass ratio is identified from the parametrical experiment.展开更多
Triple-negative breast cancer(TNBC)is a subtype of breast cancer with high mortality,and the efficacy of monotherapy for TNBC is still disappointing.Here,we developed a novel combination therapy for TNBC based on a mu...Triple-negative breast cancer(TNBC)is a subtype of breast cancer with high mortality,and the efficacy of monotherapy for TNBC is still disappointing.Here,we developed a novel combination therapy for TNBC based on a multifunctional nanohollow carbon sphere.This intelligent material contains a superadsorbed silicon dioxide sphere,sufficient loading space,a nanoscale hole on its surface,a robust shell,and an outer bilayer,and it could load both programmed cell death protein 1/programmed cell death ligand 1(PD-1/PD-L1)small-molecule immune checkpoints and small-molecule photosensitizers with excellent loading contents,protect these small molecules during the systemic circulation,and achieve accumulation of them in tumor sites after systemic administration followed by the application of laser irradiation,thereby realizing dual attack of photodynamic therapy and immunotherapy on tumors.Importantly,we integrated the fasting-mimicking diet condition that can further enhance the cellular uptake efficiency of nanoparticles in tumor cells and amplify the immune responses,further enhancing the therapeutic effect.Thus,a novel combination therapy“PD-1/PD-L1 immune checkpoint blockade+photodynamic therapy+fasting-mimicking diet”was developed with the aid of our materials,which eventually achieved a marked therapeutic effect in 4T1-tumor-bearing mice.The concept can also be applied to the clinical treatment of human TNBC with guiding significance in the future.展开更多
基金supported by the National Natural Science Foundation of China(No.11772343)the Beijing Institute of Technology Research Fund Program for Young Scholars.
文摘Staggered herringbone micromixer has shown good efficiency of mixing and performance of synthesizing nanoparticles.To bring a detailed understanding of the mixing dynamics and syn-thesis performance of this kind of micromixer,this paper carries out a high-fidelity numerical simu-lation and a parametrial experimental study on a well-established design.A passive tracer is induced in the numerical simulation to analyze mixing dynamics induced by the staggered herring-bone structures.Three effects are identified to reveal the underlying mechanisms,including folding,stretching,and splitting.To the authors’knowledge,the splitting effect is identified for the first time by the isosurface of the passive tracer,to show the high efficiency of the staggered herring-bone design.The micromixer is then used to synthesize lipid nanoparticles by mixing a mixture of lipid and poly(lactic-co-glycolic acid)(PLGA)solutions with deionized water.Under a wide mass ratio of lipid and PLGA solutions,nanoparticles with good monodispersity are synthesized to reflect the good compatibility of the micromixer and the mixture.In addition,an optimized mass ratio is identified from the parametrical experiment.
基金This work was financially supported by the National Natural Science Foundation of China(grant nos.31971307 and 32000950)Beijing Institute of Technology Research Fund Program for Young Scholars(XSQD-202213001 and grant no.3320012222215)+6 种基金the State Key Laboratory of Electrical Insulation and Power Equipment,Xi’an Jiaotong University(EIPE22208)the National Postdoctoral Program for Innovative Talents(grant no.BX20200222)the China Postdoctoral Science Foundation(grant no.2020M682878)National Natural Science Foundation of China(grant no.52202284)Zhejiang Natural Science Foundation(grant no.LQ23E020002)Wenzhou Natural Science Foundation(grant no.G20220019)cooperation between industry and education project of Ministry of Education(grant no.220601318235513).
文摘Triple-negative breast cancer(TNBC)is a subtype of breast cancer with high mortality,and the efficacy of monotherapy for TNBC is still disappointing.Here,we developed a novel combination therapy for TNBC based on a multifunctional nanohollow carbon sphere.This intelligent material contains a superadsorbed silicon dioxide sphere,sufficient loading space,a nanoscale hole on its surface,a robust shell,and an outer bilayer,and it could load both programmed cell death protein 1/programmed cell death ligand 1(PD-1/PD-L1)small-molecule immune checkpoints and small-molecule photosensitizers with excellent loading contents,protect these small molecules during the systemic circulation,and achieve accumulation of them in tumor sites after systemic administration followed by the application of laser irradiation,thereby realizing dual attack of photodynamic therapy and immunotherapy on tumors.Importantly,we integrated the fasting-mimicking diet condition that can further enhance the cellular uptake efficiency of nanoparticles in tumor cells and amplify the immune responses,further enhancing the therapeutic effect.Thus,a novel combination therapy“PD-1/PD-L1 immune checkpoint blockade+photodynamic therapy+fasting-mimicking diet”was developed with the aid of our materials,which eventually achieved a marked therapeutic effect in 4T1-tumor-bearing mice.The concept can also be applied to the clinical treatment of human TNBC with guiding significance in the future.
