@article{Che2023, 
author = {Ruijun Che and Dandan Han and Fei Wang and Huifang Liu and Miao Fan and Hongyu Yan and Tingshan Xiao and Zhaoshuo Wang and Xiaohan Zhou and Xueyi Wang and Kaihan Zhang and Caiwen Ou and Jinchao Zhang and Zhenhua Li},
title = {Liposome-coated CaO2 nanoblockers for enhanced checkpoint blockade therapy by inhibiting PD-L1 de novo biosynthesis},
year = {2023},
journal = {Nano Research},
volume = {16},
number = {5},
pages = {7227-7236},
keywords = {immune checkpoint blockade therapy, immunogenic cell death, oxygen-producing, hypoxia-inducible factor-1α (HIF-1α), programmed death ligand-1 (PD-L1) redistribution},
url = {https://www.sciopen.com/article/10.1007/s12274-022-5362-7},
doi = {10.1007/s12274-022-5362-7},
abstract = {The blocking of the immune checkpoint pathway with antibodies, especially targeting to programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway, was currently a widely used treatment strategy in clinical practice. However, the shortcomings of PD-L1 antibodies were constantly exposed with the deepening of its research and their therapeutic effect was limited by the translocation and redistribution of intracellular PD-L1. Herein, we proposed to improve immune checkpoint blockade therapy by using liposomes-coated CaO2 (CaO2@Lipo) nanoparticles to inhibit the de novo biosynthesis of PD-L1. CaO2@Lipo would produce oxygen and reduce hypoxia-inducible factor-1α (HIF-1α) level, which then downregulated the expression of PD-L1. Our in vitro and in vivo results have confirmed CaO2@Lipo promoted the degradation of HIF-1α and then downregulated the expression of PD-L1 in cancer cells for avoiding immune escape. Furthermore, to mimicking the clinical protocol of anti-PD-L1 antibodies + chemo-drugs, CaO2@Lipo was combined with doxorubicin (DOX) to investigate the tumor inhibition efficiency. We found CaO2@Lipo enhanced DOX-induced immunogenic cell death (ICD) effect, which then promoted the infiltration of T cells, strengthened the blocking effect, and thus provided an effective means to overcome the traditional immune checkpoint blockade treatment.}
}