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Iron oxide nanoparticles with sizes less than 5 nm are expected to address the long\u2010term toxicity and brain accumulation issues associated with clinical gadolinium\u2010based\n                    <jats:italic>T<\/jats:italic>\n                    <jats:sub>1<\/jats:sub>\n                    contrast agents (GBCAs) due to their non\u2010toxicity and biodegradability. However, synthesizing sub\u20105\u2010nanometer particles presents significant challenges that complicate their clinical translation. Herein, traditional iron oxide\u2010based negative (\n                    <jats:italic>T<\/jats:italic>\n                    <jats:sub>2<\/jats:sub>\n                    ) agents into positive (\n                    <jats:italic>T<\/jats:italic>\n                    <jats:sub>1<\/jats:sub>\n                    ) agents are transformed and an all\u2010in\u2010one multielement doping strategy is developed. Multiple elements into iron oxide crystals are introduced to form multielement doping engineered iron oxide nanoparticles (MDE\u2010IONPs) and their surfaces with flexible hydrophilic ligands are subsequently modified. It is shown that Ni (II) and Gd (III) doping engineered nanoparticles can effectively enhance imaging efficacy, reducing clearance rates, and enabling controlled synthesis. Ultimately, the implementation of Ni (II) and Gd (III) co\u2010engineering yield longitudinal relaxivity of up to 14.7 mM\n                    <jats:sup>\u22121<\/jats:sup>\n                    s\n                    <jats:sup>\u22121<\/jats:sup>\n                    even for particles as large as 9 nm, an improvement of approximately 300% over GBCAs. Combined with the stability, biosafety, both in vitro and in vivo results suggest that all\u2010in\u2010one multielement doping is a favorable strategy for advancing the development of next\u2010generation safe MRI contrast agents.\n                  <\/jats:p>","DOI":"10.1002\/smll.202410414","type":"journal-article","created":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T08:08:36Z","timestamp":1740125316000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Multielement Doping Engineered Iron Oxide Nanoparticles: Enabling the Shift from Negative to Positive MRI Contrast for Enhanced Diagnostic Precision"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7065-6123","authenticated-orcid":false,"given":"Chichong","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Chemistry College of Light Industry Science and Engineering Beijing Technology and Business University  Beijing 100048 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingjie","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Chemistry College of Light Industry Science and Engineering Beijing Technology and Business University  Beijing 100048 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zihan","family":"Fei","sequence":"additional","affiliation":[{"name":"Department of Chemistry College of Light Industry Science and Engineering Beijing Technology and Business University  Beijing 100048 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhijie","family":"Wang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory for Biomedical Effects of Nanomaterial and Nanosafety Institute of High Energy Physics Chinese Academy of Sciences (CAS) University of Chinese Academy of Sciences  Beijing 100049 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junjie","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Chemistry College of Light Industry Science and Engineering Beijing Technology and Business University  Beijing 100048 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruimin","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Chemistry College of Light Industry Science and Engineering Beijing Technology and Business University  Beijing 100048 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Chemistry College of Light Industry Science and Engineering Beijing Technology and Business University  Beijing 100048 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Chemistry College of Light Industry Science and Engineering Beijing Technology and Business University  Beijing 100048 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,2,21]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202318948"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-50688-0"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c03999"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202310975"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201906539"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpneph0660"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.8b01048"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202004917"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2019.03.014"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200604775"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfk062"},{"key":"e_1_2_8_12_1","first-page":"406","volume":"39","author":"Hove M. 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