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

Abstract

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 Ni 2+ . 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.

Microgels for Cell Delivery in Tissue Engineering and Regenerative Medicine

“…When they are used to pack stimulus-responsive substances, these microgels' movements can be precisely controlled, enabling targeted delivery of drugs and cells and effectively acting as microrobots [ 3 , 33 , 146 ]. Consequently, microgels are excellent carriers for the delivery and treatment of cells, bioactive substances, and drugs [ 147 , 148 ].…”

Alginate di-aldehyde-modified metal–organic framework nanocarriers as delivery platform and adjuvant in inactivated pseudorabies vaccination

“…Currently, alginate, a clinically approved natural linear copolymer with high biocompatibility, has been significantly investigated as an antigen delivery vehicle for the development of new vaccines. 29–34 Also, it has been speculated whether the advantages of polyelectrolyte alginate complexes and ZIFs can be combined to construct better vaccine adjuvants and delivery carriers. The introduction of sodium alginate can increase the water solubility of ZIFs, which is beneficial for the delivery of formulated vaccines in vivo .…”

Synergizing CXCL9 with BRD4‐PROTAC Using Nanochaperone Boosts Robust T Cell‐Dependent Antitumor Immune Responses for Cancer Immunotherapy

“…Covalent modifications (e.g., PEGylation) can improve pharmacokinetic properties of proteins, but usually with poor tumor accumulation and potentially leading to unfavorable conformation changes and loss of affinity for the target. [ 18 ] Nanoparticle‐based delivery systems, such as hydrogels, [ 19 ] liposomes, [ 20 ] polymeric micelles, [ 21 ] and inorganic nanoparticles [ 22 ] are easily functionalized in terms of formulation, encapsulation, delivery, release, and biosafety, which have been widely used to deliver proteins or small molecular drugs with various physicochemical properties. However, few of these systems are suitable to co‐deliver proteins and hydrophobic small molecular drugs because the co‐loaded hydrophobic molecules may affect the structures of protein cargos.…”