Novel Combination Therapy for Triple-Negative Breast Cancer based on an Intelligent Hollow Carbon Sphere

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.

SEMI ON-LINE SCHEDULING PROBLEM FOR MAXIMIZING THE MINIMUM MACHINE COMPLETION TIME ON TWO UNIFORM MACHINES

在这篇论文，我们在二一致 machinesM_i 上认为半是联机版本， i = 1,2，在最大的工作的处理时间预先被知道的地方。速度 s_i (s_1 = 1,1 ≤ s_2 = s ) 与机器 M_i 被联系。我们的目标是最大化 C_(min ) 。我们给 C_(min2 ) 算法并且证明它的竞争比率是至多(2s+1 )/(s+1 ) 。我们也宣称 C_(min 2 ) 算法是紧张的并且在 C_ 的竞争比率之间的差距(min 2 ) 算法和最佳的价值不比 0.555 大。我们的结果与一致，那给由，是明显的他为 s= 1。