Ni-Alginate Hydrogel Microspheres with Sustained Interleukin 2 Release to Boost Cytokine-Based Cancer Immunotherapy

Interleukin 2 (IL2) is the first approved immunotherapeutic agent in cancer treatment. However, high-dose IL2 administrated through intratumoral injection still spreads all over the body, causing serious systemic toxicity. Herein, an injectable nickel-alginate hydrogel microsphere (Ni-ALGMS) to allow effective loading of IL2 and its sustained release after intratumoral administration is reported. In this design, histidine (his)-tagged IL2 is assembled into the Ni-ALGMS via the coordination bonds between his-tag and Ni2+. After injecting IL2-loaded Ni-ALGMSs (IL2@Ni-ALGMSs) into the tumor, IL2 slowly releases over long periods, thereby avoiding the risk of cytokine storm happening in IL2 systemic administration. Applying such IL2@Ni-ALGMSs for tumor model treatment can significantly increase the tumor infiltration of T lymphocytes, and effectively inhibit tumor growth, especially in combination with immune checkpoint inhibitors. This study presents a novel IL2 sustained-releasing platform for tumor immunotherapy, which can also be conveniently applied in other cytokines-based immunotherapies.