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However, the low catalytic activity of IONPs is a major hurdle in their clinical translation. To overcome this challenge, IONPs of different compositions are examined for their Fenton reaction under pharmacologically relevant conditions. The results show that w\u00fcstite (FeO) nanoparticles exhibit higher catalytic activity than magnetite (Fe\n                    <jats:sub>3<\/jats:sub>\n                    O\n                    <jats:sub>4<\/jats:sub>\n                    ) or maghemite (\u03b3\u2010Fe\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>3<\/jats:sub>\n                    ) of matched size and coating, despite having a similar surface oxidation state. Further analyses suggest that the high catalytic activity of w\u00fcstite nanoparticles can be attributed to the presence of internal low\u2010valence iron (Fe\n                    <jats:sup>0<\/jats:sup>\n                    and Fe\n                    <jats:sup>2+<\/jats:sup>\n                    ), which accelerates the recycling of surface Fe\n                    <jats:sup>3+<\/jats:sup>\n                    to Fe\n                    <jats:sup>2+<\/jats:sup>\n                    through intraparticle electron transport. Additionally, ultrasmall w\u00fcstite nanoparticles are generated by tuning the thermodecomposition\u2010based nanocrystal synthesis, resulting in a Fenton reaction rate 5.3 times higher than that of ferumoxytol, an FDA\u2010approved IONP. Compared with ferumoxytol, w\u00fcstite nanoparticles substantially increase the level of intracellular ROS in mouse mammary carcinoma cells. This study presents a novel mechanism and pivotal improvement for the development of highly efficient ROS\u2010inducing nanozymes, thereby expanding the horizons for their therapeutic applications.\n                  <\/jats:p>","DOI":"10.1002\/smll.202305974","type":"journal-article","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T01:55:25Z","timestamp":1695952525000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Enhancing ROS\u2010Inducing Nanozyme through Intraparticle Electron Transport"],"prefix":"10.1002","volume":"20","author":[{"given":"Zhongchao","family":"Yi","sequence":"first","affiliation":[{"name":"F. Joseph Halcomb III, M.D. Department of Biomedical Engineering University of Kentucky  Lexington KY 40536 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5083-7883","authenticated-orcid":false,"given":"Xiaoyue","family":"Yang","sequence":"additional","affiliation":[{"name":"F. Joseph Halcomb III, M.D. Department of Biomedical Engineering University of Kentucky  Lexington KY 40536 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liang","sequence":"additional","affiliation":[{"name":"New York Blood Center  New York NY 10065 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny","family":"Chapelin","sequence":"additional","affiliation":[{"name":"Shu Chien \u2013 Gene Lay Department of Bioengineering &amp; Department of Radiology University of California San Diego  La Jolla CA 92093 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8632-7933","authenticated-orcid":false,"given":"Sheng","family":"Tong","sequence":"additional","affiliation":[{"name":"F. 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