LIN28B siRNA+BMN673

Malignant serous effusion (MSE) is a common and severe complication in advanced malignancies, associated with poor prognosis and high recurrence rates. To date, no standardized treatments are available for MSE management, posing significant clinical challenges. Here, we identify aberrant LIN28B expression and dysregulation of DNA repair pathways in MSE patient samples and preclinical models. We developed a nanoparticle delivery system incorporating LIN28B siRNA (siRNA/DSSP@lip-PEG-FA) to specifically inhibit LIN28B function. Combined with the PARP inhibitor BMN673, this nanoparticle system significantly alleviates MSE accumulation and prolongs survival in preclinical models without systemic cytotoxicity. Mechanistically,bulk RNA sequencing (RNAseq) of A2780 reveals that this combination therapy markedly remodels the immune microenvironment by decreasing M2 macrophages and increasing neutrophil components with altered subtypes. Notably, Arg1-positive neutrophils, which produce pro-inflammatory cytokines to increase vascular permeability, are diminished by the combination treatment. Furthermore, In vitro and in vivo experiments demonstrate that our approach inhibits vascular leakage and strengthens the rigidity of tight junction, suggesting suppression of vascular permeability. Together, our findings establish dual-targeting of PARP and LIN28B as a promising therapeutic strategy for MSE management in advanced cancers, with the potential to improve patient quality of life.