A novel prodrug and its nanoformulation suppress cancer stem cells by inducing immunogenic cell death and inhibiting indoleamine 2, 3-dioxygenase.

Abstract

Cancer stem cells (CSCs) present grand challenges for triple-negative breast cancer (TNBC). Conventional chemotherapy drugs, including Camptothecin (CPT), not only cannot eradicate CSCs but also foster a suppressive immune microenvironment for the initiation and proliferation of CSCs. Herein, we report a novel prodrug CPT-SS-NLG919 (CN) and its nanoformulation CN@PLA-HES-FA (CN@PHF), which potently suppress CSCs by regulating CSCs niche in murine TNBC 4T1 tumors. Via inducing immunogenic cell death (ICD) and simultaneous inhibiting indoleamine 2, 3-dioxygenase (IDO), CN and CN@PHF promote DC maturation, decrease Treg cells, mitigate tryptophan consumption, and reduce the amount of IL-6, IL-13, and TGF-β, converting CSCs niche to a hostile condition for CSCs to live in and eliminating CSCs efficiently, thereby inducing efficient tumor inhibition in 4T1 tumor models. Our work represents a new paradigm of eliminating CSCs by regulating tumor immune microenvironment and suggests that CN and its nanoformulation CN@PHF are promising candidates for the treatment of intractable TNBC.

• Authors: Jiankun Guan, Yuxin Wu, Xin Liu, Huimin Wang, Ningbing Ye, Zheng Li, Chen Xiao, Zhijie Zhang, Zifu Li, Xiangliang Yang
• Journal: Biomaterials (Biomaterials) Vol. 279 Pg. 121180 (12 2021) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 34768152 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• Indoleamine-Pyrrole 2,3,-Dioxygenase
• Prodrugs
• Dioxygenases

Topics

• Animals
• Cell Line, Tumor
• Dioxygenases
• Immunogenic Cell Death
• Immunotherapy
• Indoleamine-Pyrrole 2,3,-Dioxygenase
• Mice
• Neoplasms
• Neoplastic Stem Cells
• Prodrugs (pharmacology)