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.