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However, the SDT treatment efficacy is still hampered by the scarcity of ideal sonosensitizers and complex tumor microenvironment (TME). To address these challenges, a sono\u2010metabolic nano\u2010composite (TiO\n                    <jats:sub>2<\/jats:sub>\n                    \u2010Au@DON) using the metabolic reprogramming prodrugs of 6\u2010Diazo\u20105\u2010oxo\u2010l\u2010norleucine (DON) grafted on TiO\n                    <jats:sub>2<\/jats:sub>\n                    \u2010Au Janus nanoparticles (NPs) is fabricated. The coupling of TiO\n                    <jats:sub>2<\/jats:sub>\n                    and gold in the TiO\n                    <jats:sub>2<\/jats:sub>\n                    \u2010Au@DON effectively prevents the fast recombination of excited electrons and holes under ultrasound irradiation. The result is the generation of higher levels of both type I and II reactive oxygen species (ROS) compared to pure TiO\n                    <jats:sub>2<\/jats:sub>\n                    , which helps overcome the limitations of SDT in the hypoxic TME. Furthermore, the TiO\n                    <jats:sub>2<\/jats:sub>\n                    \u2010Au Janus NPs act as nano\u2010carriers, delivering DON prodrugs to the tumor site. The released DON can disrupt nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) and tumor redox homeostasis by reprogramming the metabolic pathways while it intensifies the activities of immune cells. This metabolic disruption amplifies SDT\u2010mediated oxidative stress, resulting in the increase of tumor sensitivity to ROS through TiO\n                    <jats:sub>2<\/jats:sub>\n                    \u2010Au@DON\u2010integrated synergistic effects of SDT and glutamine reprogramming strategies. This increased sensitivity ultimately induces robust immunogenic cell death (ICD), enhancing antitumor therapeutic efficacy and remodeling the tumor's immunosuppressive microenvironment.\n                  <\/jats:p>","DOI":"10.1002\/adma.202418800","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T05:57:02Z","timestamp":1739512622000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Tumor\u2010Targeted Glutamine Metabolism Blocker Synergizes with TiO\n                    <sub>2<\/sub>\n                    \u2010Au Janus Nanoparticles for Enhanced Sono\u2010Metabolic Antitumor Therapy"],"prefix":"10.1002","volume":"37","author":[{"given":"Jinling","family":"Zheng","sequence":"first","affiliation":[{"name":"Guangdong Key Laboratory of Nanomedicine Shenzhen Engineering Laboratory of nanomedicine and nanoformulations CAS\u2010HK Joint Lab for Biomaterials CAS Key Lab for Health Informatics Institute of Biomedicine and Biotechnology Shenzhen Institutes of Advanced Technology Chinese Academy of Sciences  Shenzhen 518055 P. 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