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Graphene quantum dots (GQDs) functionalized with\n                    <jats:italic>D<\/jats:italic>\n                    \u2010cysteine (\n                    <jats:italic>D<\/jats:italic>\n                    \u2010GQDs) have shown promise in inhibiting tau aggregation and transmission via \u03c0\u2013\u03c0 stacking and electrostatic interactions with tau proteins. However, the nonspecific binding of GQDs to various proteins in the physiological environment, such as serum albumin, limits their clinical translation. In this study, the aim is to enhance the specificity of\n                    <jats:italic>D<\/jats:italic>\n                    \u2010GQDs toward tau protein by incorporating a tau\u2010targeting N\u2010amino peptide, mxyl\u2010NAP2. The mxyl\u2010NAP2\/\n                    <jats:italic>D<\/jats:italic>\n                    \u2010GQD complex demonstrates improved selectivity for tau protein over serum albumin, effectively enhancing the inhibition of tau aggregation. To further minimize off\u2010target effects and optimize therapeutic delivery, the mxyl\u2010NAP2\/\n                    <jats:italic>D<\/jats:italic>\n                    \u2010GQD complex is loaded into small extracellular vesicles (sEVs), followed by functionalization of sEVs with neuron\u2010targeting ligand, rabies viral glycoprotein peptides. This strategy not only reduces off\u2010target effects, but also enhances uptake by neuron cells, which further improves inhibition of tau transmission between neurons. The results indicate that mxyl\u2010NAP2\/\n                    <jats:italic>D<\/jats:italic>\n                    \u2010GQD\u2010sEVs hold great promise for overcoming the off\u2010target limitations of\n                    <jats:italic>D<\/jats:italic>\n                    \u2010GQDs and advancing the development of precision therapeutics for neurodegenerative diseases.\n                  <\/jats:p>","DOI":"10.1002\/anbr.202500065","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T20:48:47Z","timestamp":1753217327000},"source":"Crossref","is-referenced-by-count":3,"title":["N\u2010Amino Peptide\u2013Graphene Quantum Dot Loaded Small Extracellular Vesicles for Targeted Therapy of Tauopathies"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5109-0020","authenticated-orcid":false,"given":"Runyao","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Chemical &amp; Biomolecular Engineering University of Notre Dame  Notre Dame Indiana 46556 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1502-1847","authenticated-orcid":false,"given":"Gaeun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Chemical &amp; Biomolecular Engineering University of Notre Dame  Notre Dame Indiana 46556 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin H.","family":"Rajewski","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry University of Notre Dame  Notre Dame Indiana 46556 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac J.","family":"Angera","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry University of Notre Dame  Notre Dame Indiana 46556 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan R.","family":"Del Valle","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry University of Notre Dame  Notre Dame Indiana 46556 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4353-6660","authenticated-orcid":false,"given":"Yichun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemical &amp; Biomolecular Engineering University of Notre Dame  Notre Dame Indiana 46556 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/731526"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2011.43"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000335941.68602.39"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms15034671"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1707-9"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-022-02002-0"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.554725"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-021-10573-y"},{"key":"e_1_2_8_10_1","first-page":"E4376","volume":"111","author":"Holmes B. 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