Metallo-alginate hydrogel can potentiate microwave tumor ablation for synergistic cancer treatment

Microwave ablation (MWA) as a local tumor ablation strategy suffers from posttreatment tumor recurrence. Development of adjuvant biomaterials to potentiate MWA is therefore of practical significance. Here, the high concentration of Ca²⁺ fixed by alginate as Ca²⁺-surplus alginate hydrogel shows enhanced heating efficiency and restricted heating zone under microwave exposure. The high concentration of extracellular Ca²⁺ synergizes with mild hyperthermia to induce immunogenic cell death by disrupting intracellular Ca²⁺ homeostasis. Resultantly, Ca²⁺-surplus alginate hydrogel plus MWA can ablate different tumors on both mice and rabbits at reduced operation powers. This treatment can also elicit antitumor immunity, especially if synergized with Mn²⁺, an activator of the stimulation of interferon genes pathway, to suppress the growth of both untreated distant tumors and rechallenged tumors. This work highlights that in situ-formed metallo-alginate hydrogel could act as microwave-susceptible and immunostimulatory biomaterial to reinforce the MWA therapy, promising for clinical translation.