Chemotherapy based on "Domino-effect" combined with immunotherapy amplifying the efficacy of an anti-metastatic treatment
In tumor immunotherapy, Treg cells are immunosuppressive cells. In general, the main strategy of chemo immune-therapy for Treg cells is to eliminate them using chemotherapy drugs combined with immune checkpoint inhibitors. However, the dead Treg cells still exert immunosuppressive effects via the nu...
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Published in | Journal of materials chemistry. B, Materials for biology and medicine Vol. 8; no. 39; pp. 9139 - 915 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Royal Society of Chemistry
21.10.2020
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Subjects | |
Online Access | Get full text |
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Summary: | In tumor immunotherapy, Treg cells are immunosuppressive cells. In general, the main strategy of chemo immune-therapy for Treg cells is to eliminate them using chemotherapy drugs combined with immune checkpoint inhibitors. However, the dead Treg cells still exert immunosuppressive effects
via
the nucleoside adenosine pathway. To improve immunosuppression, we designed a nanosystem to deliver synthetic chemotherapeutics and immune activators. The homemade curcumin analog (CA) was encapsulated by α-lactalbumin (α-LA), and the Treg cell specific antibody (mAb), as a therapeutic agent, was linked to the drug-loaded protein
via
matrix metalloproteinase-responded peptide (P). After the cleavage peptide responded to matrix metalloproteinase (MMP-2), the CA@α-LA-P-mAb nanoparticles were separated into CA@α-LA and antibody, which can specifically enter cancer cells and Treg cells
via
membrane fusion and Nrp-1 receptors, respectively. Finally, we found that CA can not only lead to cell death by the chondriosome apoptosis approach but also reduce the production of Treg cells by inhibiting the expression of foxp3 (a key transcription factor of Treg cells). In addition, specific antibodies can improve the immunosuppression of existing Treg cells. The combined effect of CA and antibodies amplifies the role of chemotherapy in metastatic breast cancer.
In tumor immunotherapy, Treg cells are immunosuppressive cells. |
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Bibliography: | 10.1039/d0tb01061h Electronic supplementary information (ESI) available: About CA chemical synthesis and characterization, the 4T1 cellular uptake of CA, BCA protein quantitative method, H&E staining, and the body-weight changes of mice can be discovered. See DOI ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 2050-750X 2050-7518 |
DOI: | 10.1039/d0tb01061h |