biostudies-literatureYi LNoncommunicable Chronic Diseases-National Science and Technology Major Projectthe Fundamental Research Funds for the Central UniversitiesTechnology Innovation Research and Development Project of Chengdu Science and Technology BureauNational Natural Science Foundation of ChinaSichuan Universitythe 1·3·5 Project for Disciplines of Excellence of West China HospitalSichuan Science and Technology Programe2409753https://www.ebi.ac.uk/biostudies/studies/S-EPMC11672279biostudies-literatureUnknown11(48)Temozolomide (TMZ) serves as the principal chemotherapeutic agent for glioma; nonetheless, its therapeutic efficacy is compromised by the rapid emergence of drug resistance, the inadequate targeting of glioma cells, and significant systemic toxicity. ARV-825 may play a role in modulating drug resistance by degrading the BRD4 protein, thereby exerting anti-glioma effects. Therefore, to surmount TMZ resistance and achieve efficient and specific drug delivery, a dual-targeted glutathione (GSH)-responsive nanoparticle system (T+A@Glu-NP) is designed and synthesized for the co-delivery of ARV-825 and TMZ. As anticipated, T+A@Glu-NPs significantly enhanced penetration of the blood-brain barrier (BBB), facilitated drug uptake by glioma cells, and exhibited efficient accumulation in brain tissue. Advanced science (Weinheim, Baden-Wurttemberg, Germany)BRD4 Degradation Enhanced Glioma Sensitivity to Temozolomide by Regulating Notch1 via Glu-Modified GSH-Responsive Nanoparticles.PMC11672279322220462023NSFSC1931821726302024-YF05-00576-SNZYJC210222023ZD05075002024YFFK0058SCU2024ZLYJ-1Qian ZHu YZhang ZZhou PYi LZhang YZhou WGao XGuo ACheng YfalseBRD4 Degradation Enhanced Glioma Sensitivity to Temozolomide by Regulating Notch1 via Glu-Modified GSH-Responsive Nanoparticles.Temozolomide (TMZ) serves as the principal chemotherapeutic agent for glioma; nonetheless, its therapeutic efficacy is compromised by the rapid emergence of drug resistance, the inadequate targeting of glioma cells, and significant systemic toxicity. ARV-825 may play a role in modulating drug resistance by degrading the BRD4 protein, thereby exerting anti-glioma effects. Therefore, to surmount TMZ resistance and achieve efficient and specific drug delivery, a dual-targeted glutathione (GSH)-responsive nanoparticle system (T+A@Glu-NP) is designed and synthesized for the co-delivery of ARV-825 and TMZ. As anticipated, T+A@Glu-NPs significantly enhanced penetration of the blood-brain barrier (BBB), facilitated drug uptake by glioma cells, and exhibited efficient accumulation in brain tissue. 2024-01-01T00:00:00Z2024 Dec2025-04-21T13:58:56.507Z2025-04-21T13:58:56.507ZS-EPMC116722793954415210.1002/advs.202409753