Journal
MATERIALS TODAY BIO
Volume 14, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.mtbio.2022.100284
Keywords
Immune checkpoint blockade; Immunotherapy; ROS-Responsive; Combination therapy; Synergistic effect
Funding
- National Natural Science Foundation of China [21774109, 51522304, 51973188]
- Natural Science Foundation of Zhejiang Province [LR18E030002]
- ZJU-Hangzhou Global Scientific and Technological Innovation Center [02080200-K02013002]
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In this study, a ROS-responsive synergistic delivery system was developed to enhance anticancer potency through combined chemotherapy and ICB therapy. The system could revert PTX-induced PD-L1 upregulation and significantly promote T cell infiltration, increasing tumor immunoactivating factors.
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-Ll peptide (pep) for combined chemotherapy and ICB therapy. PepPAPM@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.
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