Authors
Jinwen Zhu, Zhenzhen Guo, Renpeng Xia, Peng Miao
Published in
ACS medicinal chemistry letters. Volume 17. Issue 5. Pages 1138-1144. May 14, 2026. Epub Apr 16, 2026.
Abstract
Photo-immunotherapy combines phototherapy and immunotherapy, which can eliminate primary tumors and induce host immunity to control distant metastases. However, the effectiveness may be attenuated by the tumor defense mechanisms associated with glutamine metabolism regulation. In this work, a self-assembled stimulator was prepared for glutamine-starvation-potentiated photo-immunotherapy, which is composed of telaglenastat as the glutaminase inhibitor, chlorin e6 (Ce6) as the photosensitizer, and interferon stimulatory DNA (ISD). Ce6 transfers energy from light to molecular oxygen, generating reactive oxygen species (ROS). Telaglenastat assists in the downregulation of endogenous glutathione. Thus, ROS neutralization can be prevented, and the photodynamic therapy effect is enhanced. Additionally, the cGAS-STING signaling pathway activated by ISD remodels the tumor microenvironment by polarizing M2-type tumor-associated macrophages into M1, which finally enhances immunogenic cell death. The prepared nanomedicine combines glutamine starvation and a photo-immunotherapy strategy, offering new insights into cancer treatment.
PMID:
42157836
Bibliographic data and abstract were imported from PubMed on 14 Sep 2026.
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