期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 241, 期 -, 页码 -出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2022.114644
关键词
Photodynamic therapy; Immunotherapy; Photosensitizer; IDO; Triple negative breast cancer; Indoximod
资金
- National Health and Family Planning Commission jointly established scientific research fund
- National Natural Science Foundation of China
- Natural Science Foundation of Fujian Province
- [WKJ2016-2-14]
- [21974009]
- [2021J01549]
In this study, indoximod, an inhibitor of indoleamine 2,3-dioxygenase (IDO), was introduced to concatenate with zinc phthalocyanines (ZnPc), effectively improving the intracellular uptake and reactive oxygen species (ROS) generation of the photosensitizer 1-MT-Pc. It showed remarkable photocytotoxicity towards TNBC cells and negligible damage to normal cells, effectively inhibited the metastasis and invasion of TNBC cells, and exhibited elevated inhibitory effect on 4T1 tumor by enhanced PDT and immunotherapy.
Although photodynamic therapy (PDT) has attracted great interest, the photosensitizers in clinical had weak inhibition on metastasis and invasion of cancers. Additionally the immune response induced by PDT was insufficient to eradicate cancer. Herein, indoximod, an inhibitor of indoleamine 2,3-dioxygenase (IDO), is introduced to concatenate with zinc phthalocyanines (ZnPc) for effectively overcoming above inadequacy. Due to indoximod moiety, photosensitizer 1-MT-Pc can obtain enhanced intracellular uptake and high reactive ox-ygen species (ROS) generation. More impressively, 1-MT-Pc can achieve remarkable photocytotoxicity towards TNBC cells and negligible damage to normal cells. Meanwhile, 1-MT-Pc effectively inhibits metastasis and in-vasion of TNBC cells. Importantly, 1-MT-Pc exhibit elevated inhibitory effect on 4T1 tumor by enhanced PDT and immunotherapy.
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