Overcoming pancreatic cancer immune resistance by codelivery of CCR2 antagonist using a STING-activating gemcitabine-based nanocarrier.

ABSTRACT: STING agonist has recently gained much attention for cancer treatment, but the therapeutic potential of STING agonist is hampered by STING-associated tumor immune resistance. In this work, guided by both bioinformatics and computer modeling, we rationally designed a "one stone hits two birds" nanoparticle-based strategy to simultaneously activate STING innate immune response while eliminating STING-associated immune resistance for the treatment of pancreatic ductal adenocarcinoma (PDAC). We discovered that the ultra-small sized micellar system based on gemcitabine-conjugated polymer (PGEM), which showed superior capacity of penetration in pancreatic tumor spheroid model and orthotopic tumor model, could serve as a novel "STING agonist". The activation of STING signaling in dendritic cells

SUBMITTER: Wan Z 

PROVIDER: S-EPMC10795849 | biostudies-literature | 2023 Jan-Feb

REPOSITORIES: biostudies-literature