A synergistic cascade nanoreactor breaks bladder cancer chemoresistance: Synergizing cholesterol metabolism reprogramming with cGAS-STING-mediated metallotherapy.

Xianchun Fu, Ye Liang, Bin Xu, Chao Huang, Pengfei Zhang, Haitao Niu

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Article in Materials today. Bio, 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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5 · Who and what money

Authors and funding

6 authors.

Xianchun FuDepartment of Urology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China.

Ye LiangDepartment of Urology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China.

Bin XuDepartment of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China.

Chao HuangCollege of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, 610031, China.

Pengfei ZhangDepartment of Urology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China.

Haitao NiuDepartment of Urology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bladder cancer chemoresistance arises from a self-reinforcing vicious cycle of aberrant cholesterol metabolism and immunosuppression, which conventional single-target therapies fail to disrupt. Here, we report a folate-targeted zeolitic imidazolate framework-67 (ZIF67)-based nanoreactor termed CCZF, co-loaded with cholesterol 25-hydroxylase (CH25H) and cisplatin, to orchestrate a metabolism-chemo-immunity cascade with mutually amplifying components. First, the intrinsic catalase (CAT)-like activity of ZIF67 generates oxygen in situ to fuel CH25H-mediated cholesterol depletion that reaches 72% in resistant bladder cancer cells. This process disrupts lipid raft structure and downregulates P-glycoprotein (P-gp), resulting in 97.2% cisplatin retention in resistant cells. Second, enhanced cisplatin cytotoxicity induces nucleocytoplasmic translocation of high-mobility group box 1 (HMGB1), an early molecular signature associated with immunogenic cell death (ICD). Third, Co

Indexed as

Bladder cancercGAS-STING pathwayCholesterol 25-hydroxylaseCisplatinDrug resistanceZeolitic imidazolate framework-67

Identifiers

PMID42621345

DOI10.1016/j.mtbio.2026.103537

PMCPMC13487400

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.