ArticleNature communications2026
POLY-Senolytic nanoplatform for tumor-specific eradication of senescent tumor cells and mitigation of radiotherapy-induced immune resistance of cancer.
Yi Lai, Shunan Zhang, Jiaxing Pan, Wenyue Lan, Min Li, Zifan Zhu, Leiming Xu, Bruno G De Geest, Twan Lammers, Wen Zhang and 2 more
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In one paragraphArticle in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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12 authors.
Yi Lai *School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China.ORCID 0009-0007-2673-4618 Shunan Zhang *School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China.
Jiaxing Pan *Department of Gastroenterology, Huadong Hospital, Fudan University, Shanghai, China.
Wenyue LanState Key Laboratory of Chemical Biology & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Min LiState Key Laboratory of Chemical Biology & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Zifan ZhuSchool of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China.
Leiming XuDepartment of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Bruno G De GeestDepartment of Pharmaceutics and Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium.ORCID 0000-0001-9826-6170 Twan LammersDepartment of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, RWTH University Hospital Aachen, Aachen, Germany.ORCID 0000-0002-1090-6805 Wen ZhangSchool of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China.
Haijun YuState Key Laboratory of Chemical Biology & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. hjyu@simm.ac.cn.ORCID 0000-0002-3398-0880 Zhiai XuSchool of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China. zaxu@chem.ecnu.edu.cn.ORCID 0000-0002-4391-2507 Funding
National Natural Science Foundation of China (National Science Foundation of China) 22474042National Natural Science Foundation of China (National Science Foundation of China) 32571707National Natural Science Foundation of China (National Science Foundation of China) U22A20328; W2412035Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission) 23490712700Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission) 23ZR1475000;20430711800
6 · The paper itselfAbstract
Radiotherapy (RT) efficacy is limited by RT-induced immune resistance. Here we show that RT upregulates programmed death ligand 1 (PD-L1) on senescent tumor cells (STCs) via bromodomain-containing protein 4 (BRD4) signaling, thereby promoting immune evasion. To counter this, we develop POLY-Senolytic, a polymeric senolytic nanoparticle formed by conjugating an acid-responsive polymer to a peptide-based BRD4 PROteolysis-TArgeting Chimera via a reduction-cleavable disulfide bond. The POLY-Senolytic is activated in the acidic and reductive intracellular environment of tumor cells, leading to BRD4 degradation, suppression of RT-induced PD-L1 expression and enhanced immune clearance of STCs. Combined with RT, the POLY-Senolytic suppresses tumor growth and metastasis in orthotopic mouse models of pancreatic and breast tumors. We further engineer a β-galactosidase-responsive POLY-Tracker for real-time monitoring of senolytic therapy. Together, this study identifies an RT-driven BRD4-PD-L1 axis in STCs that promotes immune resistance and provides a practical strategy to eliminate and track them.
Indexed as
Cellular SenescenceNanoparticlesAnimalsB7-H1 AntigenBreast NeoplasmsBromodomain Containing ProteinsCell Cycle ProteinsCell Line, TumorFemaleHumansMicePancreatic NeoplasmsPolymersProteolysis Targeting ChimeraTranscription FactorsB7-H1 AntigenBRD4 protein, humanBromodomain Containing ProteinsCD274 protein, humanCell Cycle ProteinsPolymersProteolysis Targeting ChimeraTranscription Factors
Identifiers
PMID42315837
PMCPMC13434853
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