{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T16:40:00Z","timestamp":1786466400575,"version":"build-2736575974"},"reference-count":41,"publisher":"American Chemical Society (ACS)","issue":"31","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["RS-2025-16068430"],"award-info":[{"award-number":["RS-2025-16068430"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2025-02303342"],"award-info":[{"award-number":["RS-2025-02303342"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2026-25504339"],"award-info":[{"award-number":["RS-2026-25504339"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010446","name":"Institute for Basic Science","doi-asserted-by":"publisher","award":["IBS-R015-D1"],"award-info":[{"award-number":["IBS-R015-D1"]}],"id":[{"id":"10.13039\/501100010446","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cerebral ischemia induces selective neuronal death, largely due to mitochondrial dysfunction and ATP depletion. This energy crisis impairs mitophagy, exacerbates oxidative stress, and accelerates neuronal apoptosis. While exogenous ATP supplementation holds promise for restoring mitochondrial function, its clinical application is hindered by rapid in vivo clearance before brain accumulation occurs. Herein, we report positively charged ATP nanoparticles (ATP-N), formulated via electrostatic interactions with chitosan, that facilitate crossing the blood\u2013brain barrier and subsequent adsorptive-mediated transcytosis following intravenous injection, for the prevention of cerebral ischemic injury. Compared with free ATP, ATP-N exhibited a prolonged circulation time and enhanced brain accumulation. In a mouse model of cerebral ischemia, ATP-N effectively replenished intracellular ATP, restored mitochondrial membrane potential, and activated mitophagy, leading to reduced neuronal apoptosis and attenuated ischemic damage. These findings highlight ATP-N as a promising, minimally invasive therapeutic strategy to prevent ischemic brain injury, enabling rapid and efficient ATP delivery to restore mitochondrial function and promote neuronal survival.<\/jats:p>","DOI":"10.1021\/acsnano.6c05982","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:12:09Z","timestamp":1785849129000},"page":"21939-21952","source":"Crossref","is-referenced-by-count":0,"title":["Adenosine Triphosphate\nNanoparticles with Blood\u2013Brain\nBarrier Permeability for Prevention of Cerebral Ischemic Injury via\nMitochondrial Homeostasis"],"prefix":"10.1021","volume":"20","author":[{"given":"Jaewon","family":"Ju","sequence":"first","affiliation":[{"name":"Sungkyunkwan University , , ,","place":["Suwon, Republic of Korea, 16419"]},{"name":"Institute for Basic Science (IBS) , , ,","place":["Suwon, Republic of Korea, 16419"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngkwan","family":"Kim","sequence":"additional","affiliation":[{"name":"Sungkyunkwan University School of Medicine , , ,","place":["Suwon, Republic of Korea, 16419"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Ju","family":"Seo","sequence":"additional","affiliation":[{"name":"Yonsei University College of Medicine , , ,","place":["Seoul, Republic of Korea, 03722"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoonhee","family":"Jin","sequence":"additional","affiliation":[{"name":"Yonsei University College of Medicine , , ,","place":["Seoul, Republic of Korea, 03722"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jee-Yin","family":"Ahn","sequence":"additional","affiliation":[{"name":"Sungkyunkwan University School of Medicine , , ,","place":["Suwon, Republic of Korea, 16419"]},{"name":"Samsung Medical Center , , ,","place":["Seoul, Republic of Korea, 06351"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7990-5210","authenticated-orcid":true,"given":"Mikyung","family":"Shin","sequence":"additional","affiliation":[{"name":"Sungkyunkwan University , , ,","place":["Suwon, Republic of Korea, 16419"]},{"name":"Institute for Basic Science (IBS) , , ,","place":["Suwon, Republic of Korea, 16419"]},{"name":"Sungkyunkwan University , , ,","place":["Suwon, Republic of Korea, 16419"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"2026081111122957400_cit1","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1007\/BF00695577","article-title":"Delayed Neuronal Death in the Rat\nHippocampus Following Transient Forebrain Ischemia","volume":"64","author":"Kirino","year":"1984","journal-title":"Acta Neuropathol."},{"key":"2026081111122957400_cit2","doi-asserted-by":"publisher","first-page":"1977","DOI":"10.1038\/sj.emboj.7600205","article-title":"A Novel Protein-Conjugating System for Ufm1, a Ubiquitin-Fold\nModifier","volume":"23","author":"Komatsu","year":"2004","journal-title":"EMBO J."},{"key":"2026081111122957400_cit3","doi-asserted-by":"publisher","first-page":"89","DOI":"10.5483\/BMBRep.2024-0139","article-title":"PGC1\u03b1\nIs a Key Regulator of Erastin-Induced Mitochondrial Dysfunction During\nFerroptotic Cell Death","volume":"58","author":"Seok","year":"2025","journal-title":"BMB Rep."},{"key":"2026081111122957400_cit4","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/S0166-2236(99)01401-0","article-title":"Pathobiology\nof Ischaemic Stroke:\nAn Integrated View","volume":"22","author":"Dirnagl","year":"1999","journal-title":"Trends Neurosci."},{"key":"2026081111122957400_cit5","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/nrn1106","article-title":"Mechanisms,\nChallenges and Opportunities\nin Stroke","volume":"4","author":"Lo","year":"2003","journal-title":"Nat. Rev. Neurosci."},{"key":"2026081111122957400_cit6","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1038\/s41582-021-00605-6","article-title":"Pharmacological\nBrain Cytoprotection in Acute Ischaemic\nStroke - Renewed Hope in the Reperfusion Era","volume":"18","author":"Fisher","year":"2022","journal-title":"Nat. Rev. Neurol."},{"key":"2026081111122957400_cit7","doi-asserted-by":"publisher","first-page":"2142","DOI":"10.1080\/15548627.2019.1615822","article-title":"Clearance\nof Damaged\nMitochondria Via Mitophagy Is Important to the Protective Effect of\nIschemic Preconditioning in Kidneys","volume":"15","author":"Livingston","year":"2019","journal-title":"Autophagy"},{"key":"2026081111122957400_cit8","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1080\/15548627.2017.1357792","article-title":"BNIP3L\/NIX-Mediated\nMitophagy Protects Against Ischemic Brain Injury Independent of PARK2","volume":"13","author":"Yuan","year":"2017","journal-title":"Autophagy"},{"key":"2026081111122957400_cit9","doi-asserted-by":"publisher","first-page":"7552","DOI":"10.1016\/j.biomaterials.2013.06.043","article-title":"3-Hydroxybutyrate\nMethyl Ester as a Potential Drug Against Alzheimer\u2019s Disease\nVia Mitochondria Protection Mechanism","volume":"34","author":"Zhang","year":"2013","journal-title":"Biomaterials"},{"key":"2026081111122957400_cit10","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.cmet.2018.05.007","article-title":"Ubiquitination of ABCE1 by NOT4 in\nResponse to Mitochondrial Damage\nLinks Co-Translational Quality Control to PINK1-Directed Mitophagy","volume":"28","author":"Wu","year":"2018","journal-title":"Cell Metab."},{"key":"2026081111122957400_cit11","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/cdd.2012.81","article-title":"The Pathways of Mitophagy for Quality\nControl and Clearance\nof Mitochondria","volume":"20","author":"Ashrafi","year":"2013","journal-title":"Cell Death Differ."},{"key":"2026081111122957400_cit12","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.851832","article-title":"Inhibition\nof the PINK1-Parkin Pathway Enhances the Lethality of Sorafenib and\nRegorafenib in Hepatocellular Carcinoma","volume":"13","author":"Zhang","year":"2022","journal-title":"Front.\nPharmacol."},{"key":"2026081111122957400_cit13","doi-asserted-by":"publisher","first-page":"371","DOI":"10.5483\/BMBRep.2025-0014","article-title":"Ubiquitination and Ubiquitin-Like Modifications in\nMetabolic Dysfunction-Associated Steatotic Liver Disease: Mechanisms\nand Implications","volume":"58","author":"Rho","year":"2025","journal-title":"BMB Rep."},{"key":"2026081111122957400_cit14","doi-asserted-by":"publisher","first-page":"2405","DOI":"10.1007\/s00018-016-2209-y","article-title":"Regulated Cell Death\nand Adaptive Stress Responses","volume":"73","author":"Galluzzi","year":"2016","journal-title":"Cell. Mol. Life\nSci."},{"key":"2026081111122957400_cit15","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.1016\/j.jstrokecerebrovasdis.2018.01.033","article-title":"The Synergistic Neuroprotective Effects\nof Combined Rosuvastatin and Resveratrol Pretreatment Against Cerebral\nIschemia\/Reperfusion Injury","volume":"27","author":"Liu","year":"2018","journal-title":"Stroke Cerebrovasc.\nDis."},{"key":"2026081111122957400_cit16","doi-asserted-by":"publisher","first-page":"2063","DOI":"10.3892\/etm.2016.3563","article-title":"ATP-Induced Cardioprotection Against Myocardial Ischemia\/Reperfusion\nInjury Is Mediated Through the RISK Pathway","volume":"12","author":"Lian","year":"2016","journal-title":"Exp.Ther. Med."},{"key":"2026081111122957400_cit17","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2026.102640","article-title":"Hierarchically Collapsible Nanoactuator Modulates Mitochondrial Ferroptosis-Bioenergetic\nHomeostasis Cascade to Decouple Ischemic Stroke","volume":"7","author":"Sun","year":"2026","journal-title":"Cell Rep. Med."},{"key":"2026081111122957400_cit18","doi-asserted-by":"publisher","first-page":"5417","DOI":"10.1021\/acsnano.8b00477","article-title":"Bioengineered\nBoronic Ester Modified Dextran Polymer Nanoparticles as Reactive Oxygen\nSpecies Responsive Nanocarrier for Ischemic Stroke Treatment","volume":"12","author":"Lv","year":"2018","journal-title":"ACS Nano"},{"key":"2026081111122957400_cit19","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.ejpb.2022.10.011","article-title":"Lipidoid Nanoparticles Increase ATP\nUptake into Hypoxic Brain Endothelial Cells","volume":"180","author":"Khare","year":"2022","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"2026081111122957400_cit20","doi-asserted-by":"publisher","first-page":"5505","DOI":"10.1021\/acs.chemrev.3c00705","article-title":"Polymeric\nNanoparticles for Drug\nDelivery","volume":"124","author":"Beach","year":"2024","journal-title":"Chem. Rev."},{"key":"2026081111122957400_cit21","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1038\/nbt.3330","article-title":"Principles\nof Nanoparticle Design\nfor Overcoming Biological Barriers to Drug Delivery","volume":"33","author":"Blanco","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"2026081111122957400_cit22","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202003937","article-title":"Development\nof Polymeric Nanoparticles for Blood-Brain Barrier Transfer-Strategies\nand Challenges","volume":"8","author":"Zhang","year":"2021","journal-title":"Adv. Sci."},{"key":"2026081111122957400_cit23","doi-asserted-by":"publisher","first-page":"5577","DOI":"10.2147\/IJN.S36111","article-title":"The Role of\nSurface Charge in Cellular Uptake and Cytotoxicity of Medical Nanoparticles","volume":"7","author":"Fro\u0308hlich","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"2026081111122957400_cit24","doi-asserted-by":"publisher","first-page":"18732","DOI":"10.1021\/acsomega.2c01443","article-title":"Crosslinked Chitosan\u2013Gelatin Biocompatible Nanocomposite\nas a Neuro Drug Carrier","volume":"7","author":"Mathew","year":"2022","journal-title":"ACS Omega"},{"key":"2026081111122957400_cit25","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1021\/acsmacrolett.5c00374","article-title":"Enhancing Bacterial\nAdhesion with Hydro-Softened Chitosan Films","volume":"14","author":"Seo","year":"2025","journal-title":"ACS Macro Lett."},{"key":"2026081111122957400_cit26","doi-asserted-by":"publisher","first-page":"9636","DOI":"10.1021\/ac100711j","article-title":"Complete Physicochemical\nCharacterization\nof DNA\/Chitosan Complexes by Multiple Detection Using Asymmetrical\nFlow Field-Flow Fractionation","volume":"82","author":"Ma","year":"2010","journal-title":"Anal. Chem."},{"key":"2026081111122957400_cit27","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-14551-1","article-title":"Cationic Starch\/pDNA\nNanocomplexes Assembly and Their Nanostructure Changes on Gene Transfection\nEfficiency","volume":"7","author":"Wang","year":"2017","journal-title":"Sci. Rep."},{"key":"2026081111122957400_cit28","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.carbpol.2018.03.030","article-title":"Dissociation of Chitosan\/Tripolyphosphate Complexes\ninto Separate Components Upon pH Elevation","volume":"192","author":"Mazancova\u0301","year":"2018","journal-title":"Carbohydr. Polym."},{"key":"2026081111122957400_cit29","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2020.111081","article-title":"Biomolecular Uptake Effects on Chitosan\/Tripolyphosphate\nMicro- and Nanoparticle Stability","volume":"193","author":"Cai","year":"2020","journal-title":"Colloids\nSurf., B"},{"key":"2026081111122957400_cit30","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2019.115437","article-title":"A Combinatorial Study\nof Experimental Analysis and Mathematical Modeling: How Do Chitosan\nNanoparticles Deliver Therapeutics into Cells?","volume":"229","author":"Dey","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"2026081111122957400_cit31","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.01019","article-title":"Transcytosis\nto Cross the Blood Brain Barrier, New Advancements and Challenges","volume":"12","author":"Pulgar","year":"2019","journal-title":"Front. Neurosci."},{"key":"2026081111122957400_cit32","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01481-w","article-title":"The Blood-Brain Barrier: Structure,\nRegulation, and Drug Delivery","volume":"8","author":"Wu","year":"2023","journal-title":"Signal Transduct.\nTarget. Ther."},{"key":"2026081111122957400_cit33","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1208\/s12248-008-9055-2","article-title":"CNS Delivery\nVia Adsorptive Transcytosis","volume":"10","author":"Herve\u0301","year":"2008","journal-title":"AAPS J."},{"key":"2026081111122957400_cit34","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202303567","article-title":"A Cholesterol\nMetabolic Regulated Hydrogen-Bonded Organic Framework (HOF)-Based\nBiotuner for Antibody Non-Dependent Immunotherapy Tailored for Glioblastoma","volume":"35","author":"Yin","year":"2023","journal-title":"Adv. Mater."},{"key":"2026081111122957400_cit35","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-023-04763-7","article-title":"Mitochondrion-Targeted\nCarboxymethyl Chitosan Hybrid Nanoparticles Loaded with Coenzyme Q10\nProtect Cardiac Grafts Against Cold Ischaemia\u2013Reperfusion Injury\nin Heart Transplantation","volume":"21","author":"Yuan","year":"2023","journal-title":"J. Transl. Med."},{"key":"2026081111122957400_cit36","doi-asserted-by":"publisher","DOI":"10.1038\/srep01002","article-title":"PINK1-Mediated\nPhosphorylation of\nthe Parkin Ubiquitin-Like Domain Primes Mitochondrial Translocation\nof Parkin and Regulates Mitophagy","volume":"2","author":"Shiba-Fukushima","year":"2012","journal-title":"Sci. Rep."},{"key":"2026081111122957400_cit37","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1080\/15548627.2023.2259215","article-title":"PA2G4\/EBP1 Ubiquitination by PRKN\/PARKIN Promotes Mitophagy\nProtecting Neuron Death in Cerebral Ischemia","volume":"20","author":"Hwang","year":"2024","journal-title":"Autophagy"},{"key":"2026081111122957400_cit38","doi-asserted-by":"publisher","first-page":"2547","DOI":"10.1007\/s12035-017-0503-9","article-title":"Mitochondrial\nQuality Control and Disease: Insights into Ischemia-Reperfusion Injury","volume":"55","author":"Anzell","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"2026081111122957400_cit39","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.redox.2018.03.002","article-title":"Diverse Roles of\nMitochondria in\nIschemic Stroke","volume":"16","author":"Yang","year":"2018","journal-title":"Redox Biol."},{"key":"2026081111122957400_cit40","doi-asserted-by":"publisher","DOI":"10.3390\/polym14163248","article-title":"Punicalagin-Loaded\nAlginate\/Chitosan-Gallol Hydrogels for Efficient\nWound Repair and Hemostasis","volume":"14","author":"Ju","year":"2022","journal-title":"Polymers"},{"key":"2026081111122957400_cit41","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00230","article-title":"A Novel Transwell Blood\nBrain Barrier Model Using Primary Human Cells","volume":"13","author":"Stone","year":"2019","journal-title":"Front. Cell. Neurosci."}],"container-title":["ACS Nano"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsnano.6c05982","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ancac3\/article-pdf\/20\/31\/21939\/66304938\/acsnano.6c05982.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ancac3\/article-pdf\/20\/31\/21939\/66304938\/acsnano.6c05982.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T15:43:16Z","timestamp":1786462996000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ancac3\/article\/20\/31\/21939\/5235349\/Adenosine-Triphosphate-Nanoparticles-with-Blood"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,28]]},"references-count":41,"journal-issue":{"issue":"31","published-online":{"date-parts":[[2026,7,28]]},"published-print":{"date-parts":[[2026,8,11]]}},"URL":"https:\/\/doi.org\/10.1021\/acsnano.6c05982","relation":{},"ISSN":["1936-0851","1936-086X"],"issn-type":[{"value":"1936-0851","type":"print"},{"value":"1936-086X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,28]]}}}