Hydrogel Delivering All‐Trans Retinoic Acid to Regulate Macrophage Polarization to Enhance Chemo‐Immunotherapy for Gastric Cancer

Abstract As Gastric cancer is one of the most common gastrointestinal malignancies in China, with a 5‐year relative survival rate of ≈40%. Therefore, the development of new strategies to treat gastric cancer becomes urgent. In recent years, an increasing number of studies have found that all‐trans retinoic acid (Tre) can induce the polarization of M2 macrophages toward M1 in the tumor immune microenvironment (TIME), and therefore play a due role in this cancer treatment. This research proposes to load doxorubicin (DOX) and Tre in mesoporous silica, which is then loaded into sodium alginate slow‐release Gel to obtain the final product (GEL‐MSDT). Gel‐MSDT sustained‐release hydrogel can release DOX and Tre locally in tumor, kill tumor cells, induce tumor immunogenic death, regulate tumor‐associated macrophage phenotype, and promote anti‐tumor immune response. Gel‐MSDT hydrogel can coordinate chemotherapy with immunotherapy, and delay release locally to play a lasting anti‐tumor immune effect. The results of in vitro and in vivo experiments show that hydrogel can significantly inhibit tumor growth, providing an effective new strategy for the treatment of gastric cancer.