{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:10:11Z","timestamp":1792131011579,"version":"4.4.0"},"reference-count":51,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,4,18]],"date-time":"2019-04-18T00:00:00Z","timestamp":1555545600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009744","name":"Eshelman Institute for Innovation, University of North Carolina at Chapel Hill","doi-asserted-by":"publisher","award":["UNC\u201029202"],"award-info":[{"award-number":["UNC\u201029202"]}],"id":[{"id":"10.13039\/100009744","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32CA196589"],"award-info":[{"award-number":["T32CA196589"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002261","name":"Russian Foundation for Basic Research","doi-asserted-by":"publisher","award":["17\u201054\u201033027"],"award-info":[{"award-number":["17\u201054\u201033027"]}],"id":[{"id":"10.13039\/501100002261","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002261","name":"Russian Foundation for Basic Research","doi-asserted-by":"publisher","award":["18\u201029\u201009154"],"award-info":[{"award-number":["18\u201029\u201009154"]}],"id":[{"id":"10.13039\/501100002261","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Extracellular vesicles (EVs) are promising natural nanocarriers for delivery of various types of therapeutics. Earlier engineered EV\u2010based formulations for neurodegenerative diseases and cancer are reported. Herein, the use of macrophage\u2010derived EVs for brain delivery of a soluble lysosomal enzyme tripeptidyl peptidase\u20101, TPP1, to treat a lysosomal storage disorder, Neuronal Ceroid Lipofuscinoses 2 (CLN2) or Batten disease, is investigated. TPP1 is loaded into EVs using two methods: i) transfection of parental EV\u2010producing macrophages with TPP1\u2010encoding plasmid DNA (\n                    <jats:italic>p<\/jats:italic>\n                    DNA) or ii) incorporation therapeutic protein TPP1 into naive empty EVs. For the former approach, EVs released by pretransfected macrophages contain the active enzyme and TPP1\u2010encoding\n                    <jats:italic>p<\/jats:italic>\n                    DNA. To achieve high loading efficiency by the latter approach, sonication or permeabilization of EV membranes with saponin is utilized. Both methods provide proficient incorporation of functional TPP1 into EVs (EV\u2010TPP1). EVs significantly increase stability of TPP1 against protease degradation and provide efficient TPP1 delivery to target cells in in vitro model of CLN2. The majority of EV\u2010TPP1 (\u224870%) is delivered to target organelles, lysosomes. Finally, a robust brain accumulation of EV carriers and increased lifespan is recorded in late\u2010infantile neuronal ceroid lipofuscinosis (LINCL) mouse model following intraperitoneal administration of EV\u2010TPP1.\n                  <\/jats:p>","DOI":"10.1002\/adhm.201801271","type":"journal-article","created":{"date-parts":[[2019,4,18]],"date-time":"2019-04-18T04:24:14Z","timestamp":1555561454000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":140,"title":["TPP1 Delivery to Lysosomes with Extracellular Vesicles and their Enhanced Brain Distribution in the Animal Model of Batten Disease"],"prefix":"10.1002","volume":"8","author":[{"given":"Matthew J.","family":"Haney","sequence":"first","affiliation":[{"name":"Center for Nanotechnology in Drug Delivery and Carolina Institute for Nanomedicine University of North Carolina at Chapel Hill  Chapel Hill NC 27599 USA"},{"name":"Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy University of North Carolina at Chapel Hill  Chapel Hill NC 27599 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia L.","family":"Klyachko","sequence":"additional","affiliation":[{"name":"Center for Nanotechnology in Drug Delivery and Carolina Institute for Nanomedicine University of North Carolina at Chapel Hill  Chapel Hill NC 27599 USA"},{"name":"Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy University of North Carolina at Chapel Hill  Chapel Hill NC 27599 USA"},{"name":"Deparment of Chemical Enzymology Faculty of Chemistry M.V. Lomonosov Moscow State University  Moscow 119991 Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily B.","family":"Harrison","sequence":"additional","affiliation":[{"name":"Center for Nanotechnology in Drug Delivery and Carolina Institute for Nanomedicine University of North Carolina at Chapel Hill  Chapel Hill NC 27599 USA"},{"name":"Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy University of North Carolina at Chapel Hill  Chapel Hill NC 27599 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuling","family":"Zhao","sequence":"additional","affiliation":[{"name":"Center for Nanotechnology in Drug Delivery and Carolina Institute for Nanomedicine University of North Carolina at Chapel Hill  Chapel Hill NC 27599 USA"},{"name":"Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy University of North Carolina at Chapel Hill  Chapel Hill NC 27599 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander V.","family":"Kabanov","sequence":"additional","affiliation":[{"name":"Center for Nanotechnology in Drug Delivery and Carolina Institute for Nanomedicine University of North Carolina at Chapel Hill  Chapel Hill NC 27599 USA"},{"name":"Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy University of North Carolina at Chapel Hill  Chapel Hill NC 27599 USA"},{"name":"Deparment of Chemical Enzymology Faculty of Chemistry M.V. Lomonosov Moscow State University  Moscow 119991 Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9386-3790","authenticated-orcid":false,"given":"Elena V.","family":"Batrakova","sequence":"additional","affiliation":[{"name":"Center for Nanotechnology in Drug Delivery and Carolina Institute for Nanomedicine University of North Carolina at Chapel Hill  Chapel Hill NC 27599 USA"},{"name":"Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy University of North Carolina at Chapel Hill  Chapel Hill NC 27599 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,18]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920111795542633"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2016.03.023"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2009.05361.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.201701921"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2013.07.102"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg963"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0405042101"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2015.00417"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2011.164"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2010.105"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/nn402232g"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2013.11.083"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nano.2015.10.012"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nano.2017.09.011"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-014-1593-y"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2011-300449"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds317"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2012.08.008"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/mtna.2011.2"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/1478-811X-11-88"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks463"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/mtna.2013.60"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2012.180"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1129"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2013.02.019"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2011.303"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2013.12.001"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2012.08.008"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2014.04.005"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.4161\/onci.26860"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2017.01.004"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0061852"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.2217\/nnm.11.32"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0106867"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2015.03.033"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2017.07.011"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2729-04.2004"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471143030.cb0322s30"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2567"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2012.06.018"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2013.267"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.2217\/nnm.11.156"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.2217\/nnm.10.129"},{"key":"e_1_2_7_44_1","first-page":"1","volume":"4","author":"Zhao Y.","year":"2011","journal-title":"J. Nanomed. Nanotechnol."},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.5772\/61186"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23545"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201208152"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4886(03)00345-5"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07710"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2818.2006.01706.x"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.2217\/nnm.10.7"}],"container-title":["Advanced Healthcare Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fadhm.201801271","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.201801271","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/adhm.201801271","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.201801271","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T21:25:27Z","timestamp":1759785927000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adhm.201801271"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,18]]},"references-count":51,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2019,6]]}},"alternative-id":["10.1002\/adhm.201801271"],"URL":"https:\/\/doi.org\/10.1002\/adhm.201801271","archive":["Portico"],"relation":{},"ISSN":["2192-2640","2192-2659"],"issn-type":[{"value":"2192-2640","type":"print"},{"value":"2192-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,18]]},"assertion":[{"value":"2018-10-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-04-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"1801271"}}