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However, hydrophilic methionine is hardly delivered into TME due to difficult loading and rapid diffusion. Herein, the labeling assembly of methionine into nanoparticle is developed to overcome high hydrophilicity for mild\u2010heat mediated immunometabolic therapy. The strategy is to first label methionine with protocatechualdehyde (as the tag) via reversible Schiff\u2010base bond, and then drive nanoassembly of methionine (MPC@Fe) mediated by iron ions. In this fashion, a loading efficiency of 40% and assembly induced photothermal characteristics can be achieved. MPC@Fe can accumulate persistently in tumor up to 36\u00a0h due to tumor\u2010selective aggregation in acidic TME. A mild heat of 43\u00a0\u00b0C on tumor by light irradiation stimulated the immunogenic cell death and effectively generated CD8<jats:sup>+<\/jats:sup> T cells. Notably, MPC@Fe assisted by mild heat promoted 4.2\u2010fold of tumor\u2010infiltrating INF\u2010<jats:italic>\u03b3<\/jats:italic><jats:sup>+<\/jats:sup>CD8<jats:sup>+<\/jats:sup> T cells, leading to an inhibition ratio of 27.3\u2010fold versus the free methionine. Such labeling assembly provides a promising methionine delivery platform to realize mild heat mediated immunometabolic therapy, and is potentially extensible to other amino acids.<\/jats:p>","DOI":"10.1002\/adhm.202202695","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T11:48:09Z","timestamp":1673264889000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Labeling Assembly of Hydrophilic Methionine into Nanoparticle for Mild\u2010Heat Mediated Immunometabolic Therapy"],"prefix":"10.1002","volume":"12","author":[{"given":"Xiao","family":"Zheng","sequence":"first","affiliation":[{"name":"Shanghai Tenth People\u2019s Hospital, The Institute for Biomedical Engineering &amp; Nano Science Tongji University School of Medicine  Shanghai 200092 P. R. 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