Dual-targeting PARP and LIN28B alleviates the accumulation of malignant serous effusion by decreasing vascular permeability

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, single-cell RNA sequencing (scRNAseq) reveals that this combination therapy markedly remodels the immune microenvironment by decreasing M2 macrophages and increasing neutrophil components with altered subtypes.