A pH-responsive PROTAC-based nanosystem triggers tumor-specific ferroptosis to construct in situ tumor vaccines.

ABSTRACT: Bromodomain-containing protein 4 (BRD4) is a key protein that drives the development of malignant melanoma and is closely associated with the ferroptosis signaling pathway. Degradation of BRD4 can downregulate the expression of ferroptosis-related genes such as GPX4, thereby promoting tumor-specific ferroptosis. Therefore, targeting BRD4 for degradation is a promising strategy for inhibiting tumor growth. We constructed a PROTAC drug-based tumor antigen capture system to protect the activity of antigen-presenting cells (APCs) and promote antigen capture. The selected PROTAC drug (ARV-825) can specifically degrade BRD4 without harming immune cells. Specifically, magnetic nanoclusters (MNC) coated with calcium-doped manganese carbonate (Ca/MnCO₃), were used to load P

SUBMITTER: Huang L 

PROVIDER: S-EPMC11810845 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature