Figure 1.

Development of a combinatorial immunogenic nanovesicle for cancer chemoimmunotherapy. A) Schematic illustration showing the preparation of a triple therapy‐integrated nanoparticle composed of a cytotoxic polymeric gemcitabine (GEM) prodrug and a diamidobenzimidazole‐based STING agonist (diABZI) surface‐modified with an anti‐PD‐L1 antibody (αPD‐L1). The integrated nanoparticle combining these components is designated GPS based on the concatenated single initials G (GEM), P (αPD‐L1), and S (STING agonist). αPD‐L1 conjugation not only augments cellular uptake and intratumor drug delivery but also improves the overall antitumor efficacy. B) Upon systemic administration, cytotoxic GEM induces cancer cell apoptosis to generate tumor cell debris, while the diABZI agonist activates the STING signaling pathway to induce DC maturation, cell debris uptake, and cytokine release. These events transform an immunosuppressed “cold” tumor microenvironment (TME) into a “hot” TME and result in robust immune activation, which can further synergize with immune checkpoint blockade with an anti‐PD‐L1 antibody (αPD‐L1).