Mitoxantrone‐Encapsulated ZIF‐8 Enhances Chemo‐Immunotherapy via Amplified Immunogenic Cell Death
Junhong Li, Wenxing Lv, Ziwei Han, Yike Li, Jinqi Deng, Yanjuan Huang, Shuo Wan, Jiashu Sun, Bo Dai
Abstract
Abstract Chemo‐immunotherapy, combining systemic chemotherapeutic drugs and immune checkpoint blockers, is a promising paradigm in cancer treatment. However, challenges such as limited induction of immune responses and systemic immune toxicity have hindered its clinical applications. Here, a zeolite imidazolate framework‐8 (ZIF‐8) that encapsulates mitoxantrone (MIT), an immune cell death (ICD)‐inducing chemotherapeutic agent (MIT@ZIF‐8), is synthesized using a one‐pot aqueous‐phase process. ZIF‐8 serves as a dual‐functional nanomaterial for chemo‐immunotherapy: a carrier to enhance tumor uptake of MIT for improved chemotherapy efficacy, and a pyroptosis inducer to amplify MIT‐induced ICD for augmented anti‐tumor immune responses. As a result, in vivo administration of MIT@ZIF‐8 markedly inhibits tumor growth in both immunologically “hot” colon cancer and immunologically “cold” prostate cancer. Moreover, MIT@ZIF‐8 treatment increases the abundance of cytotoxic CD8 + T cells and reduces the amount of immunosuppressive regulatory T cells in tumors, thereby enhancing anti‐tumor immunity and sensitizing prostate cancer to anti‐CTLA‐4 immunotherapy. In summary, MIT@ZIF‐8 offers a highly translational approach for chemo‐immunotherapy.