| Autor: |
Che, Ruijun, Han, Dandan, Wang, Fei, Liu, Huifang, Fan, Miao, Yan, Hongyu, Xiao, Tingshan, Wang, Zhaoshuo, Zhou, Xiaohan, Wang, Xueyi, Zhang, Kaihan, Ou, Caiwen, Zhang, Jinchao, Li, Zhenhua |
| Předmět: |
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| Zdroj: |
Nano Research; May2023, Vol. 16 Issue 5, p7227-7236, 10p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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