Advanced Healthcare Materials, Год журнала: 2025, Номер unknown

Опубликована: Май 28, 2025

Abstract Pyroptosis‐immunotherapy has potential for triple‐negative breast cancer treatment, but its efficacy is limited by insufficient pyroptosis activation and the need phased, balanced, spatially controlled of active species during long‐term treatment. To reconcile intracellular/extracellular demands in tumor ablation, a nanoparticle‐hydrogel hybrid enabling spatiotemporal reactive oxygen (ROS) modulation engineered. An open‐shell sonosensitizer with unpaired electrons molecular orbitals prepared chelating Cu 2 ⁺ TCPP. These sonosensitizers are undergoing bovine serum albumin mediated biomineralization to form calcium phosphate particles incorporated into an injectable hydrogel through Schiff base crosslinking between dopamine‐functionalized oxidized hyaluronic acid gallic acid‐modified chitosan. After intratumoral injection, nanoparticles endocytosed cells undergo acidic degradation, releasing ions GSH‐activatable sonosensitizers. Calcium overload synergizes ultrasound‐mediated oxidative stress induce mitochondrial damage pyroptosis, while adhesive hydrogels retained extracellular matrix control excessive secondary ROS levels protect oxidation‐sensitive entities. This dual‐action mechanism enhances overall therapeutic effect combining immediate killing immune activation. study provides new route material design, addressing conflicting short‐term ablation activation, overcoming limitations current pyroptosis‐based immunotherapies.

Язык: Английский