Combining cisplatin and a STING agonist into one molecule for metalloimmunotherapy of cancer.

ABSTRACT: Mounting evidence suggests that strategies combining DNA-damaging agents and stimulator of interferon genes (STING) agonists are promising cancer therapeutic regimens because they can amplify STING activation and remodel the immunosuppressive tumor microenvironment. However, a single molecular entity comprising both agents has not yet been developed. Herein, we designed two Pt^IV-MSA-2 conjugates (I and II) containing the DNA-damaging chemotherapeutic drug cisplatin and the innate immune-activating STING agonist MSA-2; these conjugates showed great potential as multispecific small-molecule drugs against pancreatic cancer. Mechanistic studies revealed that conjugate I upregulated the expression of transcripts associated with innate immunity and metabolism in c

SUBMITTER: Zhang S 

PROVIDER: S-EPMC10852989 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature