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ER-Targeting Cyanine Dye as an NIR Photoinducer to Efficiently Trigger Photoimmunogenic Cancer Cell Death
时间:2022-03-03 16:09:45
分类:JACS
作品信息

期刊

Journal of the American Chemical Society

标题

ER-Targeting Cyanine Dye as an NIR Photoinducer to Efficiently Trigger Photoimmunogenic Cancer Cell Death

作者

He Ma, Yang Lu, Zhibin Huang, Saran Long, Jianfang Cao, Zhen Zhang, Xiao Zhou, Chao Shi, Wen Sun, Jianjun Du, Jiangli Fan, and Xiaojun Peng

摘要

Endoplasmic reticulum (ER) stress, caused by overproduction of reactive oxygen species (ROS), has been shown to be responsible for immunogenic cell death (ICD). Seeking ROS generator targeting ER is an optimal solution to efficiently induce ER stress. Despite clear indications of demand for ER-targeting photosensitizer, the alternative chemical tools remain limited. Herein, the first ER-localizable ICD photoinducer using thio-pentamethine cyanine dye (TCy5) to induce ER stress under mild near-infrared (NIR) irradiation has been developed. Within the ICD photoinducer design, polyfluorinated TCy5-Ph-3F possesses a selective tropism to ER accumulation and superior ROS generation capability in both normoxia and hypoxia conditions, which benefit from its low singlet–triplet gaps. Under NIR irradiation, cancer cells stained by TCy5-Ph-3F will lead to ER stress and induce massive emission of damage-associated molecular patterns, including calreticulin and heat-shock protein 70 exposure, high mobility group box 1 efflux, and adenosine triphosphate secretion. Dendritic cells maturation and CD8+ T cells activation in vivo also highlight the effectiveness. Therefore, the growth of abscopal tumors was substantially suppressed by the primary tumor treated with TCy5-Ph-3F and NIR irradiation. These results confer practical applicability that could provide a guideline for designing efficient ICD photoinducers, which will enable expanding organic molecular applications for cancer immunotherapy.

原文链接

https://pubs.acs.org/doi/10.1021/jacs.1c11886

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