PARPi Combining Nanoparticle LIN28B siRNA for the Management of Malignant Ascites - Research article

Sep 23, 2026

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Malignant serous effusion (MSE), including malignant pleural effusion (MPE) and malignant ascites (MA), is a common severe complication in advanced malignancies with poor prognosis and frequent recurrence. No standardized MSE therapies exist, creating major clinical challenges. Elevated LIN28B expression and dysregulated DNA repair pathways are identified as key features. A targeted siRNA nanoparticle (siLin28B/DSSP@lip-PEG-FA) combined with the PARP inhibitor BMN673 shows synergistic antitumor activity, reducing MA accumulation and extending survival in a preclinical ovarian cancer model without systemic cytotoxicity.

LanguageEnglish

CategoryResearch & Report

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Pages20

Reading Time50 min

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Introduction

Current clinical challenges and unmet needs in malignant ascites management

Standard therapies and limitations

Advanced Science [www.advancedscience.com](www.advancedscience.com) RESEARCH ARTICLE PARPi Combining Nanoparticle LIN28B siRNA for the Management of Malignant Ascites Yan Fang1, 2, 3 Qian Shen4 Yao Lin5 Jing Zhu6 Xiaolan Zhu6 Rui Huang1, 2, 3 Yijia Wu1, 2 Feiyang Shen1, 2 Qian Li1, 2, 3 Guopei Zheng1, 2, 3 Zhe Zhang1, 2, 3 Qian Chu4 Junhao Hu6 Jianfeng Shen1, 2, 3 1 Department of Ophthalmology, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China 2 Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China 3 Institute of Translational Medicine, National Facility for Translational Medicine, Shanghai Jiao Tong University, Shanghai, China 4 Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 5 Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China 6 Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing, China Correspondence: Qian Chu ([qianchu@tjh.tjmu.edu.cn](qianchu@tjh.tjmu.edu.cn)) Junhao Hu (jhhu@sioc.ac.cn) Jianfeng Shen (jfshen@shsmu.edu.cn) Received: 9 June 2025 Revised: 23 December 2025 Accepted: 3 January 2026 Keywords: malignant ascites | nanoparticle LIN28B siRNA | neutrophil | PARP inhibitor | vascular permeability ABSTRACT Malignant serous effusion (MSE), including malignant pleural effusion (MPE) and malignant ascites (MA), is a common and severe complication in advanced malignancies, associated with poor prognosis and high recurrence rates. Currently, no standardized treatments are available for MSE management, posing significant clinical challenges. Here, we identify elevated LIN28B expression and dysregulation of DNA repair pathways as two major features associated with MSE from patient and preclinical samples. We develop a targeted siRNA nanoparticle delivery system (siLin28B/DSSP@lip-PEG-FA) in combination with the PARP inhibitor BMN673, providing a synergistic therapeutic strategy against MSE. This combination significantly alleviated MA accumulation and prolonged survival in a preclinical ovarian cancer (OC) model without causing systemic cytotoxicity. Mechanistically, single-cell RNA sequencing (scRNA-seq) revealed that this combination therapy markedly remodeled the immune microenvironment by decreasing M2 macrophages and neutrophil populations with altered subtypes. Notably, Arg1-positive neutrophils, producing pro-inflammatory cytokines to increase vascular permeability, were diminished after the combination treatment. Furthermore, in vitro and in vivo experiments demonstrated that suppression of PARP and LIN28B inhibited vascular leakage and reinforced tight junction integrity. Collectively, our findings highlight dual targeting of PARP and LIN28B as a promising MA management approach in patients with advanced cancers, with the potential to improve patient quality of life. | Abbreviations: ALT, aspartate alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; CEACAM, Carcinoembryonic Antigen-Related Cell Adhesion Molecule; CLSM, confocal laser scanning microscopy; CNVs, copy number variations; CopyKAT, Copy number Karyotyping of Aneuploid Tumors; CREA, creatinine; DEGs, differentially expressed genes; GO, Gene Ontology; GO-BP, Gene Ontology Biological Process; GSEA, gene set enrichment analysis; GSH, glutathione; H2 O2 , hydrogen peroxide; IR, infrared; MA, malignant ascites; MPE, malignant pleural effusion; MSE, Malignant serous effusion; NGS, Next-generation sequencing; OC, ovarian cancer; PBS, phosphate-buffered saline; scRNA-seq, single-cell RNA sequencing; SNVs, single nucleotide variations; TBIL, total bilirubin; TCBA, thiocystamine bisacrylamide; UA, uric acid; VEGF, vascular endo

FAQs

What clinical problem does the study address?

The study addresses malignant serous effusion, especially malignant ascites, which is life-threatening and associated with poor prognosis and high recurrence rates.

How is the treatment strategy designed in the study?

It combines a targeted LIN28B siRNA nanoparticle delivery system (siLin28B/DSSP@lip-PEG-FA) with the PARP inhibitor BMN673.

What therapeutic effects are reported in preclinical models?

The combination significantly alleviates malignant ascites accumulation and prolongs survival in a preclinical ovarian cancer model, without causing systemic cytotoxicity.

Sep 23, 2026

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