Nucleic acid-based delivery system delivering platinum drugs cooperates with siRNA for potentiated chemo-immunotherapy by reducing phosphatidylserine exposure and activating the cGAS-STING pathway.

ABSTRACT: Chemotherapeutic drugs, such as cisplatin and phenanthriplatin (PhenPt), as STING agonists to induce DNA damage and activate the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway provides a potential strategy for clinical chemo-immunotherapy. However, treatment with Pt-based drugs leads to irreversible ectopia of phosphatidylserine (PS), a major component of the intracellular membrane, to the surface of the cancer cells by enzymes (Xkr8). Exposed PS can bind to immune cell receptors and inhibit the presentation of tumor antigens, leading to immunosuppression and attenuation of chemotherapy. Herein, we report a novel approach to enhance chemo-immunotherapy by constructing siRNA targeted Xkr8 (siXkr8)-mediated tetrahedral framework nucleic acid nanogel str

SUBMITTER: Yan J 

PROVIDER: S-EPMC12541582 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature