Cancer-associated fibroblasts (CAFs) play a crucial role in creating an immunosuppressive environment and remodeling the extracellular matrix within
tumors, leading to
chemotherapy resistance and limited immune cell infiltration. To address these challenges, integrating CAFs deactivation into immunogenic
chemotherapy may represent a promising approach to the reversal of immune-excluded
tumor. We developed a
tumor-targeted nanomedicine called the
glutathione-responsive nanocomplex (GNC). The GNC co-loaded
dasatinib, a CAF inhibitor, and
paclitaxel, a chemotherapeutic agent, to deactivate CAFs and enhance the effects of immunogenic
chemotherapy. Due to the modification with
hyaluronic acid, the GNC preferentially accumulated in the
tumor periphery and responsively released cargos, mitigating the
tumor stroma as well as overcoming chemoresistance. Moreover, GNC treatment exhibited remarkable immunostimulatory efficacy, including CD8+ T cell expansion and PD-L1 downregulation, facilitating
immune checkpoint blockade therapy. In summary, the integration of CAF deactivation and immunogenic
chemotherapy using the GNC nanoplatform holds promise for rebuilding immune-excluded
tumors.