Remote-Controllable Immune-Priming Spot Formation Via Nanocomplexed Hydrogel-Assisted Histotripsy: Immunoasis.

Abstract

Immunotherapy, which harnesses the immune system to eliminate cancer cells, offers durable, and specific responses. However, many tumors exhibit "immune deserts" - immunosuppressive microenvironments with low T cell infiltration due to the dominance of suppressive myeloid cells and limited inflammatory cues. Cancer vaccines combining tumor antigens and adjuvants can potentially convert these immune deserts into immune-active lesions. Yet, systemic administration often leads to adverse effects such as cytokine storms and off-target immune activation. To address this, we propose "Immunoasis", a spatiotemporally controllable immunotherapeutic system. This platform integrates injectable, adjuvant-loaded hydrogels with externally triggered boiling histotripsy. The hydrogel enables prolonged local retention of immunostimulatory payloads, while histotripsy disrupts tumor tissues and induces in situ conversion of the gel into nanocomplexes enriched with antigens and adjuvants. This localized activation enhances antigen presentation and promotes T cell recruitment at the tumor site. The tunable nature of the ultrasound stimulus provides flexible treatment scheduling and supports personalized cancer therapy. By establishing immune-priming niches within the tumor, Immunoasis effectively transforms immune deserts into immune-responsive microenvironments, enhancing antitumor immunity and improving therapeutic efficacy.