{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:56:26Z","timestamp":1792443386664,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"30","license":[{"start":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T00:00:00Z","timestamp":1656547200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81872806"],"award-info":[{"award-number":["81872806"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013314","name":"Higher Education Discipline Innovation Project","doi-asserted-by":"publisher","award":["B18035"],"award-info":[{"award-number":["B18035"]}],"id":[{"id":"10.13039\/501100013314","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alzheimer's disease (AD), as a progressive and irreversible brain disorder, remains the most universal neurodegenerative disease. No effective therapeutic methods are established yet due to the hindrance of the blood\u2010brain barrier (BBB) and the complex pathological condition of AD.\u00a0 Therefore, a multifunctional nanocarrier (Rapa@DAK\/siRNA) for AD treatment is\u00a0constructed to achieve small interfering RNA of \u03b2\u2010site precursor protein (APP) cleaving enzyme\u20101\u00a0(BACE1 siRNA) and rapamycin co\u2010delivery into the brain, based on <jats:italic>Aleuria aurantia<\/jats:italic> lectin (AAL) and \u03b2\u2010amyploid\u00a0(A\u03b2)\u2010binding peptides (KLVFF) modified PEGylated dendrigraft poly\u2010<jats:sc>l<\/jats:sc>\u2010lysines (DGLs) via intranasal administration. Nasal administration provides an effective way to deliver drugs directly into the brain through the nose\u2010to\u2010brain pathway. AAL, specifically binding to L\u2010fucose located in the olfactory epithelium, endows\u00a0Rapa@DAK\/siRNA with high brain entry efficiency through intranasal administration. KLVFF peptide as an A\u03b2 targeting ligand and aggregation inhibitor enables\u00a0nanoparticles to bind with A\u03b2, inhibit A\u03b2 aggregation, and reduce toxicity. Meanwhile, the release of BACE1 siRNA and rapamycin is\u00a0confirmed to reduce BACE1 expression, promote autophagy, and reduce A\u03b2 deposition. Rapa@DAK\/siRNA is\u00a0verified to improve the cognition of transgenic AD mice after intranasal administration. Collectively, the multifunctional nanocarrier provides\u00a0an effective and potential intranasal avenue for combination therapy of AD.<\/jats:p>","DOI":"10.1002\/smll.202203182","type":"journal-article","created":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T13:40:42Z","timestamp":1656596442000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":136,"title":["Intranasal Delivery of BACE1 siRNA and Rapamycin by Dual Targets Modified Nanoparticles for Alzheimer's Disease Therapy"],"prefix":"10.1002","volume":"18","author":[{"given":"Xiaotong","family":"Yang","sequence":"first","affiliation":[{"name":"Key Laboratory of Drug\u2010Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant\u2010Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology West China School of Pharmacy Sichuan University  No. 17, Block 3, Southern Renmin Road Chengdu 610041 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqin","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Drug\u2010Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant\u2010Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology West China School of Pharmacy Sichuan University  No. 17, Block 3, Southern Renmin Road Chengdu 610041 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Xia","sequence":"additional","affiliation":[{"name":"Key Laboratory of Drug\u2010Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant\u2010Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology West China School of Pharmacy Sichuan University  No. 17, Block 3, Southern Renmin Road Chengdu 610041 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Lei","sequence":"additional","affiliation":[{"name":"Key Laboratory of Drug\u2010Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant\u2010Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology West China School of Pharmacy Sichuan University  No. 17, Block 3, Southern Renmin Road Chengdu 610041 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihang","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Drug\u2010Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant\u2010Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology West China School of Pharmacy Sichuan University  No. 17, Block 3, Southern Renmin Road Chengdu 610041 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenfeng","family":"Jia","sequence":"additional","affiliation":[{"name":"Key Laboratory of Drug\u2010Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant\u2010Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology West China School of Pharmacy Sichuan University  No. 17, Block 3, Southern Renmin Road Chengdu 610041 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Drug\u2010Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant\u2010Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology West China School of Pharmacy Sichuan University  No. 17, Block 3, Southern Renmin Road Chengdu 610041 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo","family":"Cheng","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Translational Medicine Center for Translational Medicine Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University) Ministry of Education Department of Pediatrics West China Second University Hospital Sichuan University  Chengdu Sichuan 610041 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5355-7238","authenticated-orcid":false,"given":"Huile","family":"Gao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Drug\u2010Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant\u2010Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology West China School of Pharmacy Sichuan University  No. 17, Block 3, Southern Renmin Road Chengdu 610041 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,30]]},"reference":[{"key":"e_1_2_8_1_1","unstructured":"S.Gauthier P.Rosa\u2010Neto J. A.Morais C.Webster Alzheimer's Disease International https:\/\/www.alzint.org\/resource\/world-alzheimer-report-2021\/(accessed: September2021)."},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119129"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2009.09.002"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2021.04.008"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202004025"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy132"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(76)91936-X"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(91)90052-2"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(91)90609-V"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M808759200"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-019-0132-6"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.201909999"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173361"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112180"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2020.10.015"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1307152110"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2022.02.001"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2018.06.024"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2018.05.011"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2021.02.012"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2007.03.039"},{"key":"e_1_2_8_22_1","first-page":"781","volume":"67","author":"Gheri G.","year":"1991","journal-title":"Boll. \u2010 Soc. Ital. Biol. Sper."},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2004.11.052"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201600064"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10719-008-9135-7"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cclet.2020.09.009"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-016-0386-8"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2020.00137"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-014-1379-7"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2018.1556946"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.11.095"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2018.04.034"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.8b03644"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04255-z"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2017.05.005"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2021.04.022"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2015.11.060"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2005.03.020"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6215(03)00021-1"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2020.02.011"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2006.12.006"}],"container-title":["Small"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/smll.202203182","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/smll.202203182","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/smll.202203182","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T22:22:29Z","timestamp":1692829349000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/smll.202203182"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,30]]},"references-count":41,"journal-issue":{"issue":"30","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["10.1002\/smll.202203182"],"URL":"https:\/\/doi.org\/10.1002\/smll.202203182","archive":["Portico"],"relation":{},"ISSN":["1613-6810","1613-6829"],"issn-type":[{"value":"1613-6810","type":"print"},{"value":"1613-6829","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,30]]},"assertion":[{"value":"2022-05-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2203182"}}