Light-controlled pyroptosis via redox-responsive microneedles enhances photodynamic-epigenetic immunotherapy in breast cancer.

ABSTRACT: Despite the potential of photodynamic therapy in breast cancer treatment, inadequate immunogenicity and inefficient pyroptosis induction remain critical limitations. To address this, we developed dissolvable microneedles (MNs) for localized co-delivery of decitabine (DEC) and glutathione (GSH)-responsive photosensitizer nanoparticles (HPPH-ss-NPs), aiming to potentiate immunogenic pyroptosis in breast cancer. The MNs enabled spatiotemporal control of DEC (dissolution-dependent release) and HPPH-ss-NPs (GSH-triggered activation), enhancing tumor drug levels with reduced systemic exposure. Mechanistically, DEC restored pyroptosis executioner gasdermin E (GSDME) expression, while HPPH-ss-NPs depleted intracellular GSH and generated caspase-3-activating ROS under light irradiation. The synergi

SUBMITTER: Yu H 

PROVIDER: S-EPMC12536554 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature