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Photothermal therapy (PTT) has recently shown promise as an effective treatment for gliomas. However, nonspecific accumulation of photothermal agents may affect adjacent normal brain structures, and the inflammatory response induced during PTT may result in an increased risk of brain tumor recurrence or metastasis. Here, the design and fabrication of an intelligent nanomachine is reported based on Gd\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>3<\/jats:sub>\n                    @Ir\/TMB\u2010RVG29 (G@IT\u2010R) hybrid nanomaterials. These nanomaterials enable tumor\u2010specific PTT and eliminate inflammation to protect normal brain tissue. The mechanism involves the rabies virus glycopeptide\u201029 peptide (RVG29) passing through the blood\u2013brain barrier (BBB) and targeting gliomas. In the tumor microenvironment, Ir nanozymes can act as logic control systems to trigger chromogenic reaction amplification of 3,3\u2032,5,5\u2032\u2010tetramethylbenzidine (TMB) for tumor\u2010specific PTT, whereas in normal brain tissues, they scavenge reactive oxygen species (ROS) generated by poor therapy and function as protective agents. Autophagy inhibition of Gd\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>3<\/jats:sub>\n                    enables excellent photothermal therapeutic effects on orthotopic gliomas and protection against inflammation in normal cells. The results of this study may prove useful in developing highly efficient nanomedicines for glioma treatment.\n                  <\/jats:p>","DOI":"10.1002\/advs.202204937","type":"journal-article","created":{"date-parts":[[2022,11,27]],"date-time":"2022-11-27T23:19:30Z","timestamp":1669591170000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Modulating Nanozyme\u2010Based Nanomachines via Microenvironmental Feedback for Differential Photothermal Therapy of Orthotopic Gliomas"],"prefix":"10.1002","volume":"10","author":[{"given":"Na","family":"Yin","sequence":"first","affiliation":[{"name":"State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied Chemistry Chinese Academy of Sciences  Changchun Jilin 130022 China"},{"name":"School of Applied Chemistry and Engineering University of Science and Technology of China  Hefei Anhui 230026 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