{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:55:50Z","timestamp":1792709750287,"version":"4.5.0"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sig Transduct Target Ther"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Dysregulated autophagy is a hallmark of Alzheimer\u2019s disease (AD), yet the extent of impairment in macroautophagy and chaperone-mediated autophagy (CMA) remains unclear. Here, we show that both pathways are disrupted in AD model mice, preceding \u03b2-amyloid accumulation and driving disease progression. However, therapeutic autophagy modulation is severely restricted by the blood\u2013brain barrier (BBB). To overcome this, we developed Microglia-Liposome Fusion Extrusion (MiLi-FE), a method to engineer microglia-derived nanovesicles (AR@ENV) for the codelivery of AR7 (a CMA inducer) and rapamycin (a macroautophagy inducer). Leveraging its microglial membrane origin, AR@ENV effectively crosses the BBB and targets inflammatory sites in the AD brain, where it is internalized by neurons. Once inside, they synchronously activate both autophagy pathways: AR7 antagonizes retinoic acid receptor alpha (RAR\u03b1) to enhance CMA, while rapamycin inhibits mTOR to promote macroautophagy. This coordinated activation enhances clearance of \u03b2-amyloid and other toxic aggregates, restores proteostasis, and provides robust neuroprotection. Furthermore, the strategy ameliorates neuroinflammation and significantly rescues cognitive deficits in two distinct AD mouse models. By integrating synchronized dual autophagy activation with targeted biomimetic delivery, AR@ENV represents a promising therapeutic candidate for AD. Moreover, the MiLi-FE platform offers a versatile and scalable approach for delivering diverse therapeutics to the central nervous system, extending its potential applicability to a range of neurological disorders.<\/jats:p>","DOI":"10.1038\/s41392-025-02453-y","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T04:13:14Z","timestamp":1762143194000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Microglia-derived nanovesicles synchronize macroautophagy and chaperone-mediated autophagy for Alzheimer\u2019s disease therapy"],"prefix":"10.1038","volume":"10","author":[{"given":"Min","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7911-9551","authenticated-orcid":false,"given":"Yang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingrui","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingke","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"key":"2453_CR1","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1016\/j.cell.2012.02.040","volume":"148","author":"Y Huang","year":"2012","unstructured":"Huang, Y. & Mucke, L. Alzheimer mechanisms and therapeutic strategies. Cell 148, 1204\u20131222 (2012).","journal-title":"Cell"},{"key":"2453_CR2","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1146\/annurev.neuro.24.1.1121","volume":"24","author":"VM Lee","year":"2001","unstructured":"Lee, V. M., Goedert, M. & Trojanowski, J. Q. Neurodegenerative tauopathies. Annu. Rev. Neurosci. 24, 1121\u20131159 (2001).","journal-title":"Annu. Rev. Neurosci."},{"key":"2453_CR3","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/s41572-021-00269-y","volume":"7","author":"DS Knopman","year":"2021","unstructured":"Knopman, D. S. et al. Alzheimer disease. Nat. Rev. Dis. Prim. 7, 33 (2021).","journal-title":"Nat. Rev. Dis. Prim."},{"key":"2453_CR4","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1038\/nm.3232","volume":"19","author":"RA Nixon","year":"2013","unstructured":"Nixon, R. A. The role of autophagy in neurodegenerative disease. Nat. Med. 19, 983\u2013997 (2013).","journal-title":"Nat. Med."},{"key":"2453_CR5","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1016\/S1474-4422(18)30238-2","volume":"17","author":"A Scrivo","year":"2018","unstructured":"Scrivo, A., Bourdenx, M., Pampliega, O. & Cuervo, A. M. Selective autophagy as a potential therapeutic target for neurodegenerative disorders. Lancet Neurol. 17, 802\u2013815 (2018).","journal-title":"Lancet Neurol."},{"key":"2453_CR6","doi-asserted-by":"crossref","unstructured":"Li, W. et al. Turnover atlas of proteome and phosphoproteome across mouse tissues and brain regions. Cell 188, 2267\u20132287.e21 (2025).","DOI":"10.1016\/j.cell.2025.02.021"},{"key":"2453_CR7","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1016\/j.jconrel.2024.01.047","volume":"367","author":"B Singh","year":"2024","unstructured":"Singh, B., Day, C. M., Abdella, S. & Garg, S. Alzheimer\u2019s disease current therapies, novel drug delivery systems and future directions for better disease management. J. Control Rel. 367, 402\u2013424 (2024).","journal-title":"J. Control Rel."},{"key":"2453_CR8","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s40035-025-00465-w","volume":"14","author":"BH Kim","year":"2025","unstructured":"Kim, B. H. et al. Second-generation anti-amyloid monoclonal antibodies for Alzheimer\u2019s disease: current landscape and future perspectives. Transl. Neurodegener. 14, 6 (2025).","journal-title":"Transl. Neurodegener."},{"key":"2453_CR9","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1056\/NEJMoa2212948","volume":"388","author":"CH van Dyck","year":"2023","unstructured":"van Dyck, C. H. et al. Lecanemab in early Alzheimer\u2019s disease. N. Engl. J. Med. 388, 9\u201321 (2023).","journal-title":"N. Engl. J. Med."},{"key":"2453_CR10","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1001\/jama.2023.13239","volume":"330","author":"JR Sims","year":"2023","unstructured":"Sims, J. R. et al. Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial. JAMA 330, 512\u2013527 (2023).","journal-title":"JAMA"},{"key":"2453_CR11","doi-asserted-by":"publisher","first-page":"4414","DOI":"10.1093\/brain\/awad188","volume":"146","author":"H Hampel","year":"2023","unstructured":"Hampel, H. et al. Amyloid-related imaging abnormalities (ARIA): radiological, biological and clinical characteristics. Brain 146, 4414\u20134424 (2023).","journal-title":"Brain"},{"key":"2453_CR12","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/s41392-024-01911-3","volume":"9","author":"J Zhang","year":"2024","unstructured":"Zhang, J. et al. Recent advances in Alzheimer\u2019s disease: mechanisms, clinical trials and new drug development strategies. Sig. Transduct. Target Ther. 9, 211 (2024).","journal-title":"Sig. Transduct. Target Ther."},{"key":"2453_CR13","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1016\/j.neuron.2017.01.022","volume":"93","author":"FM Menzies","year":"2017","unstructured":"Menzies, F. M. et al. Autophagy and neurodegeneration: pathogenic mechanisms and therapeutic opportunities. Neuron 93, 1015\u20131034 (2017).","journal-title":"Neuron"},{"key":"2453_CR14","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1038\/s41593-022-01084-8","volume":"25","author":"JH Lee","year":"2022","unstructured":"Lee, J. H. et al. Faulty autolysosome acidification in Alzheimer\u2019s disease mouse models induces autophagic build-up of Abeta in neurons, yielding senile plaques. Nat. Neurosci. 25, 688\u2013701 (2022).","journal-title":"Nat. Neurosci."},{"key":"2453_CR15","doi-asserted-by":"publisher","first-page":"2696","DOI":"10.1016\/j.cell.2021.03.048","volume":"184","author":"M Bourdenx","year":"2021","unstructured":"Bourdenx, M. et al. Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome. Cell 184, 2696\u20132714.e2625 (2021).","journal-title":"Cell"},{"key":"2453_CR16","doi-asserted-by":"crossref","unstructured":"Caballero, B. et al. Interplay of pathogenic forms of human tau with different autophagic pathways. Aging Cell 17, e12692 (2018).","DOI":"10.1111\/acel.12692"},{"key":"2453_CR17","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1126\/science.1101738","volume":"305","author":"AM Cuervo","year":"2004","unstructured":"Cuervo, A. M., Stefanis, L., Fredenburg, R., Lansbury, P. T. & Sulzer, D. Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy. Science 305, 1292\u20131295 (2004).","journal-title":"Science"},{"key":"2453_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22501-9","volume":"12","author":"B Caballero","year":"2021","unstructured":"Caballero, B. et al. Acetylated tau inhibits chaperone-mediated autophagy and promotes tau pathology propagation in mice. Nat. Commun. 12, 2238 (2021).","journal-title":"Nat. Commun."},{"key":"2453_CR19","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1038\/s41580-024-00757-5","volume":"25","author":"RA Nixon","year":"2024","unstructured":"Nixon, R. A. & Rubinsztein, D. C. Mechanisms of autophagy-lysosome dysfunction in neurodegenerative diseases. Nat. Rev. Mol. Cell Biol. 25, 926\u2013946 (2024).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2453_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.addr.2019.11.009","volume":"165-166","author":"R Pandit","year":"2020","unstructured":"Pandit, R., Chen, L. & Gotz, J. The blood-brain barrier: physiology and strategies for drug delivery. Adv. Drug Deliv. Rev. 165-166, 1\u201314 (2020).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"2453_CR21","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/s41392-023-01481-w","volume":"8","author":"D Wu","year":"2023","unstructured":"Wu, D. et al. The blood-brain barrier: structure, regulation, and drug delivery. Sig. Transduct. Target Ther. 8, 217 (2023).","journal-title":"Sig. Transduct. Target Ther."},{"key":"2453_CR22","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.jconrel.2020.02.042","volume":"321","author":"X Wang","year":"2020","unstructured":"Wang, X. et al. Autophagy inhibition changes the disposition of non-viral gene carriers during blood-brain barrier penetration and enhances TRAIL-induced apoptosis in brain metastatic tumor. J. Control Rel. 321, 497\u2013508 (2020).","journal-title":"J. Control Rel."},{"key":"2453_CR23","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1038\/nri.2017.125","volume":"18","author":"Q Li","year":"2018","unstructured":"Li, Q. & Barres, B. A. Microglia and macrophages in brain homeostasis and disease. Nat. Rev. Immunol. 18, 225\u2013242 (2018).","journal-title":"Nat. Rev. Immunol."},{"key":"2453_CR24","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/j.neuron.2019.08.028","volume":"104","author":"DH Gutmann","year":"2019","unstructured":"Gutmann, D. H. & Kettenmann, H. Microglia\/brain macrophages as central drivers of brain tumor pathobiology. Neuron 104, 442\u2013449 (2019).","journal-title":"Neuron"},{"key":"2453_CR25","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ade0293","volume":"9","author":"C Wang","year":"2023","unstructured":"Wang, C. et al. Secreted endogenous macrosomes reduce Abeta burden and ameliorate Alzheimer\u2019s disease. Sci. Adv. 9, eade0293 (2023).","journal-title":"Sci. Adv."},{"key":"2453_CR26","doi-asserted-by":"publisher","first-page":"e3000159","DOI":"10.1371\/journal.pbio.3000159","volume":"17","author":"LA Green","year":"2019","unstructured":"Green, L. A., Nebiolo, J. C. & Smith, C. J. Microglia exit the CNS in spinal root avulsion. PLoS Biol. 17, e3000159 (2019).","journal-title":"PLoS Biol."},{"key":"2453_CR27","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.jconrel.2016.09.016","volume":"241","author":"D Ingato","year":"2016","unstructured":"Ingato, D., Lee, J. U., Sim, S. J. & Kwon, Y. J. Good things come in small packages: overcoming challenges to harness extracellular vesicles for therapeutic delivery. J. Control Rel. 241, 174\u2013185 (2016).","journal-title":"J. Control Rel."},{"key":"2453_CR28","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1038\/s41565-021-00931-2","volume":"16","author":"IK Herrmann","year":"2021","unstructured":"Herrmann, I. K., Wood, M. J. A. & Fuhrmann, G. Extracellular vesicles as a next-generation drug delivery platform. Nat. Nanotechnol. 16, 748\u2013759 (2021).","journal-title":"Nat. Nanotechnol."},{"key":"2453_CR29","doi-asserted-by":"publisher","first-page":"1839","DOI":"10.1038\/s41590-023-01627-6","volume":"24","author":"Z Yin","year":"2023","unstructured":"Yin, Z. et al. APOE4 impairs the microglial response in Alzheimer\u2019s disease by inducing TGFbeta-mediated checkpoints. Nat. Immunol. 24, 1839\u20131853 (2023).","journal-title":"Nat. Immunol."},{"key":"2453_CR30","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1126\/science.aad8373","volume":"352","author":"S Hong","year":"2016","unstructured":"Hong, S. et al. Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science 352, 712\u2013716 (2016).","journal-title":"Science"},{"key":"2453_CR31","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1038\/s41586-019-1088-4","volume":"568","author":"JV Pluvinage","year":"2019","unstructured":"Pluvinage, J. V. et al. CD22 blockade restores homeostatic microglial phagocytosis in ageing brains. Nature 568, 187\u2013192 (2019).","journal-title":"Nature"},{"key":"2453_CR32","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202211055","volume":"35","author":"X Wang","year":"2023","unstructured":"Wang, X. et al. Albumin-hitchhiking drug delivery to tumor-draining lymph nodes precisely boosts tumor-specific immunity through autophagy modulation of immune cells. Adv. Mater. 35, e2211055 (2023).","journal-title":"Adv. Mater."},{"key":"2453_CR33","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/S0169-409X(98)00090-8","volume":"36","author":"N Bodor","year":"1999","unstructured":"Bodor, N. & Buchwald, P. Recent advances in the brain targeting of neuropharmaceuticals by chemical delivery systems. Adv. Drug Deliv. Rev. 36, 229\u2013254 (1999).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"2453_CR34","doi-asserted-by":"publisher","first-page":"5033","DOI":"10.1021\/acsnano.2c12840","volume":"17","author":"D Huang","year":"2023","unstructured":"Huang, D. et al. Multiscale NIR-II imaging-guided brain-targeted drug delivery using engineered cell membrane nanoformulation for Alzheimer\u2019s disease therapy. ACS Nano 17, 5033\u20135046 (2023).","journal-title":"ACS Nano"},{"key":"2453_CR35","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/j.jconrel.2021.05.045","volume":"335","author":"H Xiang","year":"2021","unstructured":"Xiang, H. et al. Novel brain-targeting 3-n-butylphthalide prodrugs for ischemic stroke treatment. J. Control Rel. 335, 498\u2013514 (2021).","journal-title":"J. Control Rel."},{"key":"2453_CR36","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41591-018-0297-y","volume":"25","author":"DA Nation","year":"2019","unstructured":"Nation, D. A. et al. Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction. Nat. Med. 25, 270\u2013276 (2019).","journal-title":"Nat. Med."},{"key":"2453_CR37","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1038\/s41591-020-0886-4","volume":"26","author":"JW Blanchard","year":"2020","unstructured":"Blanchard, J. W. et al. Reconstruction of the human blood-brain barrier in vitro reveals a pathogenic mechanism of APOE4 in pericytes. Nat. Med. 26, 952\u2013963 (2020).","journal-title":"Nat. Med."},{"key":"2453_CR38","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1038\/nature11087","volume":"485","author":"RD Bell","year":"2012","unstructured":"Bell, R. D. et al. Apolipoprotein E controls cerebrovascular integrity via cyclophilin A. Nature 485, 512\u2013516 (2012).","journal-title":"Nature"},{"key":"2453_CR39","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1016\/j.neuron.2023.12.003","volume":"112","author":"Z Lv","year":"2024","unstructured":"Lv, Z. et al. Clearance of beta-amyloid and synapses by the optogenetic depolarization of microglia is complement selective. Neuron 112, 740\u2013754 e747 (2024).","journal-title":"Neuron"},{"key":"2453_CR40","doi-asserted-by":"publisher","first-page":"1596","DOI":"10.1016\/j.cell.2013.11.030","volume":"155","author":"CN Parkhurst","year":"2013","unstructured":"Parkhurst, C. N. et al. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell 155, 1596\u20131609 (2013).","journal-title":"Cell"},{"key":"2453_CR41","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202304687","volume":"11","author":"X Zhong","year":"2024","unstructured":"Zhong, X. et al. Cordycepin modulates microglial M2 polarization coupled with mitochondrial metabolic reprogramming by targeting HKII and PDK2. Adv. Sci. 11, e2304687 (2024).","journal-title":"Adv. Sci."},{"key":"2453_CR42","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23260-3","volume":"12","author":"C Dong","year":"2021","unstructured":"Dong, C., Madar, A. D. & Sheffield, M. E. J. Distinct place cell dynamics in CA1 and CA3 encode experience in new environments. Nat. Commun. 12, 2977 (2021).","journal-title":"Nat. Commun."},{"key":"2453_CR43","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1146\/annurev-pharmtox-051921-013930","volume":"64","author":"LF Locskai","year":"2024","unstructured":"Locskai, L. F., Alyenbaawi, H. & Allison, W. T. Antiepileptic drugs as potential dementia prophylactics following traumatic brain injury. Annu. Rev. Pharm. Toxicol. 64, 577\u2013598 (2024).","journal-title":"Annu. Rev. Pharm. Toxicol."},{"key":"2453_CR44","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1038\/s41593-020-0687-6","volume":"23","author":"MA Busche","year":"2020","unstructured":"Busche, M. A. & Hyman, B. T. Synergy between amyloid-beta and tau in Alzheimer\u2019s disease. Nat. Neurosci. 23, 1183\u20131193 (2020).","journal-title":"Nat. Neurosci."},{"key":"2453_CR45","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1038\/nrd.2018.109","volume":"17","author":"B Boland","year":"2018","unstructured":"Boland, B. et al. Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing. Nat. Rev. Drug Discov. 17, 660\u2013688 (2018).","journal-title":"Nat. Rev. Drug Discov."},{"key":"2453_CR46","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/bs.acc.2022.09.006","volume":"112","author":"J Simren","year":"2023","unstructured":"Simren, J., Elmgren, A., Blennow, K. & Zetterberg, H. Fluid biomarkers in Alzheimer\u2019s disease. Adv. Clin. Chem. 112, 249\u2013281 (2023).","journal-title":"Adv. Clin. Chem."},{"key":"2453_CR47","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1007\/s00401-018-1932-x","volume":"136","author":"JL Molinuevo","year":"2018","unstructured":"Molinuevo, J. L. et al. Current state of Alzheimer\u2019s fluid biomarkers. Acta Neuropathol. 136, 821\u2013853 (2018).","journal-title":"Acta Neuropathol."},{"key":"2453_CR48","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1212\/WNL.0000000000001859","volume":"85","author":"D Alcolea","year":"2015","unstructured":"Alcolea, D. et al. Amyloid precursor protein metabolism and inflammation markers in preclinical Alzheimer disease. Neurology 85, 626\u2013633 (2015).","journal-title":"Neurology"},{"key":"2453_CR49","doi-asserted-by":"publisher","first-page":"3422","DOI":"10.1021\/acs.nanolett.8b04148","volume":"19","author":"N Perets","year":"2019","unstructured":"Perets, N. et al. Golden exosomes selectively target brain pathologies in neurodegenerative and neurodevelopmental disorders. Nano Lett. 19, 3422\u20133431 (2019).","journal-title":"Nano Lett."},{"key":"2453_CR50","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/ncb2979","volume":"16","author":"A Stolz","year":"2014","unstructured":"Stolz, A., Ernst, A. & Dikic, I. Cargo recognition and trafficking in selective autophagy. Nat. Cell Biol. 16, 495\u2013501 (2014).","journal-title":"Nat. Cell Biol."},{"key":"2453_CR51","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1038\/s41590-025-02198-4","volume":"26","author":"HD Mason","year":"2025","unstructured":"Mason, H. D. et al. Granzyme K(+) CD8 T cells slow tauopathy progression by targeting microglia. Nat. Immunol. 26, 1152\u20131167 (2025).","journal-title":"Nat. Immunol."},{"key":"2453_CR52","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39181-2","volume":"14","author":"L Wang","year":"2023","unstructured":"Wang, L. et al. Bioinspired engineering of fusogen and targeting moiety equipped nanovesicles. Nat. Commun. 14, 3366 (2023).","journal-title":"Nat. Commun."},{"key":"2453_CR53","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202002160","volume":"32","author":"X Wang","year":"2020","unstructured":"Wang, X. et al. On-demand autophagy cascade amplification nanoparticles precisely enhanced oxaliplatin-induced cancer immunotherapy. Adv. Mater. 32, e2002160 (2020).","journal-title":"Adv. Mater."},{"key":"2453_CR54","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1016\/j.apsb.2023.10.009","volume":"14","author":"Y Li","year":"2024","unstructured":"Li, Y. et al. Multidimensional autophagy nano-regulator boosts Alzheimer\u2019s disease treatment by improving both extra\/intraneuronal homeostasis. Acta Pharm. Sin. B 14, 1380\u20131399 (2024).","journal-title":"Acta Pharm. Sin. B"}],"container-title":["Signal Transduction and Targeted Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41392-025-02453-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-025-02453-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-025-02453-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T05:02:32Z","timestamp":1762146152000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41392-025-02453-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,3]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2453"],"URL":"https:\/\/doi.org\/10.1038\/s41392-025-02453-y","relation":{},"ISSN":["2059-3635"],"issn-type":[{"value":"2059-3635","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,3]]},"assertion":[{"value":"2 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 September 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 September 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 November 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"360"}}