1. A ROS-responsive synergistic delivery system for combined immunotherapy and chemotherapy
- Author
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Doudou Hu, Wei Zhang, Jiajia Xiang, Dongdong Li, Yong Chen, Pengcheng Yuan, Shiqun Shao, Zhuxian Zhou, Youqing Shen, and Jianbin Tang
- Subjects
Immune checkpoint blockade ,Immunotherapy ,ROS-Responsive ,Combination therapy ,Synergistic effect ,Medicine (General) ,R5-920 ,Biology (General) ,QH301-705.5 - Abstract
Immune checkpoint blockade (ICB) therapies that target programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway are currently used for the treatment of various cancer types. However, low response rates of ICB remain the major issue and limit their applications in clinic. Here, we developed a ROS-responsive synergistic delivery system (pep-PAPM@PTX) by integrating physically-encapsulated paclitaxel (PTX) and surface-modified anti-PD-L1 peptide (pep) for combined chemotherapy and ICB therapy. Pep-PAPM@PTX could bind the cell surface PD-L1 and drive its recycling to lysosomal degradation, thus reverting PTX-induced PD-L1 upregulation and downregulating PD-L1 expression. As a result, pep-PAPM@PTX significantly promoted T cell infiltration and increased tumor immunoactivating factors, synergizing PTX chemotherapy to achieve enhanced anticancer potency in a triple-negative breast cancer (TNBC) model.
- Published
- 2022
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