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To regulate photophysical properties, previous fumaronitrile-core fluorophore designs primarily employed electron-donating structure modifications and \u03c0-conjugation extension strategies. Here, we report a novel strategy to enhance the fluorescence performance of fluorophores by introducing methyl groups into fumaronitrile phenyl rings. The introduction of methyl groups reduces the ability to generate reactive oxygen species while enhancing the fluorescence quantum yield. Notably, after encapsulating DSPE-PEG2000 to form nanoparticles, TFN-Me nanoparticles exhibited superior fluorescence performance than previously reported fluorophores and successfully applied in in vivo tumor fluorescence imaging. This study indicates that the methyl introduction strategy holds the potential to become a powerful tool for developing high-brightness fluorophores with fumaronitrile structure.<\/jats:p>","DOI":"10.3390\/molecules30142898","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T11:58:07Z","timestamp":1751975887000},"page":"2898","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Methylsteric Effects Enhance Fluorescence in Diphenylfumaronitrile AIEgens"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5317-1537","authenticated-orcid":false,"given":"Zihao","family":"Xu","sequence":"first","affiliation":[{"name":"Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenwen","family":"Ma","sequence":"additional","affiliation":[{"name":"Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuchen","family":"Song","sequence":"additional","affiliation":[{"name":"Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Tian","sequence":"additional","affiliation":[{"name":"Institute of Molecular Aggregation Science, Tianjin University, Tianjin 300072, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5180-4963","authenticated-orcid":false,"given":"Fang","family":"Hu","sequence":"additional","affiliation":[{"name":"Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6794-217X","authenticated-orcid":false,"given":"Wenbo","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Molecular Aggregation Science, Tianjin University, Tianjin 300072, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liu","family":"Cai","sequence":"additional","affiliation":[{"name":"Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wang, K., Guo, R., Chen, X.Y., Yang, Y.S., Qiao, L.Q., and Wang, M.L. 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