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Graphene quantum dots (GQDs) functionalized with\n                  <jats:italic>D<\/jats:italic>\n                  - cysteine (\n                  <jats:italic>D<\/jats:italic>\n                  -GQDs) have shown promise in inhibiting tau aggregation and transmission\n                  <jats:italic>via<\/jats:italic>\n                  \u03c0-\u03c0 stacking and electrostatic interactions with tau proteins. However, the non-specific binding of GQDs to various proteins in the physiological environment, such as serum albumin, limits their clinical translation. In this study, we aim to enhance the specificity of\n                  <jats:italic>D<\/jats:italic>\n                  -GQDs toward tau protein by incorporating a tau-targeting N- amino peptide, mxyl-NAP2. The mxyl-NAP2\/\n                  <jats:italic>D<\/jats:italic>\n                  -GQD complex demonstrated improved selectivity for tau protein over serum albumin, effectively enhancing the inhibition of tau aggregation. To further minimize off-target effects and optimize therapeutic delivery, we loaded the mxyl-NAP2\/\n                  <jats:italic>D<\/jats:italic>\n                  -GQD complex into small extracellular vesicles (sEVs), followed by functionalization of sEVs with neuron targeting ligand, rabies viral glycoprotein peptides. This strategy not only reduced off-target effects, but also enhanced uptake by neuron cells, which further improved inhibition of tau transmission between neurons. Our results indicated that mxyl-NAP2\/\n                  <jats:italic>D<\/jats:italic>\n                  -GQD-loaded sEVs hold great promise for overcoming the off-target limitations of\n                  <jats:italic>D<\/jats:italic>\n                  - GQDs and advancing the development of precision therapeutics for neurodegenerative diseases.\n                <\/jats:p>","DOI":"10.1101\/2024.12.23.630154","type":"posted-content","created":{"date-parts":[[2024,12,26]],"date-time":"2024-12-26T02:25:19Z","timestamp":1735179919000},"source":"Crossref","is-referenced-by-count":1,"title":["N-Amino Peptide-Graphene Quantum Dot Loaded Small Extracellular Vesicles for Targeted Therapy of Tauopathies"],"prefix":"10.64898","author":[{"given":"Runyao","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaeun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin H.","family":"Rajewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac J.","family":"Angera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan R.","family":"Del Valle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4353-6660","authenticated-orcid":false,"given":"Yichun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2024122622540037000_2024.12.23.630154v1.1","first-page":"731526","volume":"2012","year":"2012","journal-title":"Int J Alzheimers Dis"},{"key":"2024122622540037000_2024.12.23.630154v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2011.43"},{"key":"2024122622540037000_2024.12.23.630154v1.3","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000335941.68602.39"},{"key":"2024122622540037000_2024.12.23.630154v1.4","doi-asserted-by":"publisher","DOI":"10.3390\/ijms15034671"},{"key":"2024122622540037000_2024.12.23.630154v1.5","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1707-9"},{"key":"2024122622540037000_2024.12.23.630154v1.6","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-022-02002-0"},{"key":"2024122622540037000_2024.12.23.630154v1.7","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.554725"},{"key":"2024122622540037000_2024.12.23.630154v1.8","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-021-10573-y"},{"key":"2024122622540037000_2024.12.23.630154v1.9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1411649111"},{"key":"2024122622540037000_2024.12.23.630154v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70088-2"},{"key":"2024122622540037000_2024.12.23.630154v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2011.03.006"},{"key":"2024122622540037000_2024.12.23.630154v1.12","doi-asserted-by":"crossref","unstructured":"K. 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