In:
Chemical Science, Royal Society of Chemistry (RSC), Vol. 14, No. 22 ( 2023), p. 5956-5964
Kurzfassung:
Controllable activation of the innate immune adapter protein – stimulator of interferon genes (STING) pathway is a critical challenge for the clinical development of STING agonists due to the potential “on-target off-tumor” toxicity caused by systematic activation of STING. Herein, we designed and synthesized a photo-caged STING agonist 2 with a tumor cell-targeting carbonic anhydrase inhibitor warhead, which could be readily uncaged by blue light to release the active STING agonist leading to remarkable activation of STING signaling. Furthermore, compound 2 was found to preferentially target tumor cells, stimulate the STING signaling in zebrafish embryo upon photo-uncaging and to induce proliferation of macrophages and upregulation of the mRNA expression of STING as well as its downstream NF-kB and cytokines, thus leading to significant suppression of tumor cell growth in a photo-dependent manner with reduced systemic toxicity. This photo-caged agonist not only provides a powerful tool to precisely trigger STING signalling, but also represents a novel controllable STING activation strategy for safer cancer immunotherapy.
Materialart:
Online-Ressource
ISSN:
2041-6520
,
2041-6539
Sprache:
Englisch
Verlag:
Royal Society of Chemistry (RSC)
Publikationsdatum:
2023
ZDB Id:
2559110-1
