{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T14:43:40Z","timestamp":1782139420003,"version":"3.54.5"},"reference-count":28,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82030049"],"award-info":[{"award-number":["82030049"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81973248"],"award-info":[{"award-number":["81973248"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82302267"],"award-info":[{"award-number":["82302267"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32170989"],"award-info":[{"award-number":["32170989"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Open Project Program of the Key Lab of Smart Drug Delivery"},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"crossref","award":["ZA2021MH141"],"award-info":[{"award-number":["ZA2021MH141"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Bone marrow-derived mesenchymal stem cell exosomes (EXOs) are attractive in biotechnology and biomedical research, as they possess natural cell-targeting properties and can cross biological barriers by influencing the SDF-1\/CXCR4 axis. Lipid calcium phosphate (LCP) consists of a calcium phosphate core and an asymmetric phospholipid bilayer containing abundant Ca2+ ions. AMD3100 modification of targeted LCP (T-LCP) can achieve targeted delivery to ischemic lesions via specific binding to CXCR4 receptors on various neuronal cell surfaces. Methods: Herein, a fused membrane formulation that simultaneously possesses EXO characteristics and enables targeted modification with AMD3100 was produced. The characteristics of biologically derived EXOs, artificially designed T-LCP, and the fused membrane formulation, including targeted delivery and gene loading efficiency, were then compared. Results: The fusion of artificially designed T-LCP with EXOs of natural origin is feasible and combines the advantages of both to achieve more prominent targeted delivery effects. Conclusions: MiRNA210-based gene therapy was effective in this study and provides a strategy for therapeutic efficacy in delivery systems with different targeting efficiencies.<\/jats:p>","DOI":"10.3390\/pharmaceutics17101357","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T13:42:03Z","timestamp":1761054123000},"page":"1357","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Fused Membrane-Targeted Nanoscale Gene Delivery System Based on an Asymmetric Membrane Structure for Ischemic Stroke"],"prefix":"10.3390","volume":"17","author":[{"given":"Jing","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmaceutical Sciences, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education & State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmaceutical Sciences, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education & State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2888-404X","authenticated-orcid":false,"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmaceutical Sciences, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education & State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zitong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmaceutical Sciences, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education & State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9761-9915","authenticated-orcid":false,"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China"},{"name":"Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China"},{"name":"Institute of Nuclear Medicine and Molecular Imaging, Zhejiang University, Hangzhou 310058, China"},{"name":"Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou 310009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Mi","sequence":"additional","affiliation":[{"name":"Precision Medicine Research Center, School of Pharmacy, Binzhou Medical University, Yantai 264003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaowei","family":"Xu","sequence":"additional","affiliation":[{"name":"Precision Medicine Research Center, School of Pharmacy, Binzhou Medical University, Yantai 264003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhua","family":"Yang","sequence":"additional","affiliation":[{"name":"Precision Medicine Research Center, School of Pharmacy, Binzhou Medical University, Yantai 264003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3708-6090","authenticated-orcid":false,"given":"Jing","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, School of Pharmaceutical Sciences, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education & State Key Laboratory of Advanced Drug Formulations for Overcoming Delivery Barriers, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China"},{"name":"Department of Nuclear Medicine and PET Center, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China"},{"name":"Institute of Nuclear Medicine and Molecular Imaging, Zhejiang University, Hangzhou 310058, China"},{"name":"Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou 310009, China"},{"name":"Key Laboratory for Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou 310027, China"},{"name":"College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"113518","DOI":"10.1016\/j.expneurol.2020.113518","article-title":"Emerging neuroprotective strategies for the treatment of ischemic stroke: An overview of clinical and preclinical studies","volume":"335","author":"Paul","year":"2021","journal-title":"Exp. Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Liu, W., Liu, L., Li, H., Xie, Y., Bai, J., Guan, J., Qi, H., and Sun, J. (2024). Targeted pathophysiological treatment of ischemic stroke using nanoparticle-based drug delivery system. J. Nanobiotechnol., 22.","DOI":"10.1186\/s12951-024-02772-2"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2862","DOI":"10.1021\/acsabm.2c00246","article-title":"M1 Macrophage-Derived Exosome-Mimetic Nanovesicles with an Enhanced Cancer Targeting Ability","volume":"5","author":"Baek","year":"2022","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.omtn.2020.06.013","article-title":"Therapeutic Effects of Simultaneous Delivery of Nerve Growth Factor mRNA and Protein via Exosomes on Cerebral Ischemia","volume":"21","author":"Yang","year":"2020","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8814239","DOI":"10.1155\/2020\/8814239","article-title":"Exosomes Derived from CXCR4-Overexpressing BMSC Promoted Activation of Microvascular Endothelial Cells in Cerebral Ischemia\/Reperfusion Injury","volume":"2020","author":"Li","year":"2020","journal-title":"Neural Plast."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3100","DOI":"10.1111\/cas.14563","article-title":"Biology and therapeutic potential of mesenchymal stem cell-derived exosomes","volume":"111","author":"Xunian","year":"2020","journal-title":"Cancer Sci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Rajput, A., Varshney, A., Bajaj, R., and Pokharkar, V. (2022). Exosomes as New Generation Vehicles for Drug Delivery: Biomedical Applications and Future Perspectives. Molecules, 27.","DOI":"10.3390\/molecules27217289"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lu, M., and Huang, Y. (2020). Bioinspired exosome-like therapeutics and delivery nanoplatforms. Biomaterials, 242.","DOI":"10.1016\/j.biomaterials.2020.119925"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Sun, L., Fan, M., Huang, D., Li, B., Xu, R., Gao, F., and Chen, Y. (2021). Clodronate-loaded liposomal and fibroblast-derived exosomal hybrid system for enhanced drug delivery to pulmonary fibrosis. Biomaterials, 271.","DOI":"10.1016\/j.biomaterials.2021.120761"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.jconrel.2011.10.020","article-title":"Calcium phosphate nanoparticles with an asymmetric lipid bilayer coating for siRNA delivery to the tumor","volume":"158","author":"Li","year":"2012","journal-title":"J. Control Release"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1023\/B:HIJO.0000032355.66152.b8","article-title":"CXCR4-SDF-1 signalling, locomotion, chemotaxis and adhesion","volume":"35","author":"Kucia","year":"2004","journal-title":"J. Mol. Histol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Zhao, R., Liu, J., Li, Z., Zhang, W., Wang, F., and Zhang, B. (2022). Recent Advances in CXCL12\/CXCR4 Antagonists and Nano-Based Drug Delivery Systems for Cancer Therapy. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14081541"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.7150\/thno.52570","article-title":"Engineering exosomes for targeted drug delivery","volume":"11","author":"Liang","year":"2021","journal-title":"Theranostics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1158\/0008-5472.CAN-21-2269","article-title":"Nanoparticle Delivery of miR-122 Inhibits Colorectal Cancer Liver Metastasis","volume":"82","author":"Sendi","year":"2022","journal-title":"Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Wang, Q., Chen, Y., Meng, L., Yin, J., Wang, L., and Gong, T. (2022). A Novel Perspective on Ischemic Stroke: A Review of Exosome and Noncoding RNA Studies. Brain Sci., 12.","DOI":"10.3390\/brainsci12081000"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"144764","DOI":"10.1016\/j.gene.2020.144764","article-title":"Exosomes derived from miRNA-210 overexpressing bone marrow mesenchymal stem cells protect lipopolysaccharide induced chondrocytes injury via the NF-\u03baB pathway","volume":"751","author":"He","year":"2020","journal-title":"Gene"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1097\/FPC.0000000000000499","article-title":"Bone marrow mesenchymal stem cell-derived exosomes carrying E3 ubiquitin ligase ITCH attenuated cardiomyocyte apoptosis by mediating apoptosis signal-regulated kinase-1","volume":"33","author":"Li","year":"2023","journal-title":"Pharmacogenet Genom."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e005052","DOI":"10.1161\/JAHA.116.005052","article-title":"MicroRNA-210 Promotes Accumulation of Neural Precursor Cells Around Ischemic Foci After Cerebral Ischemia by Regulating the SOCS1-STAT3-VEGF-C Pathway","volume":"7","author":"Meng","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1161\/01.STR.20.1.84","article-title":"Reversible middle cerebral artery occlusion without craniectomy in rats","volume":"20","author":"Longa","year":"1989","journal-title":"Stroke"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2875","DOI":"10.1161\/STROKEAHA.119.026652","article-title":"Validity and Reliability of Neurological Scores in Mice Exposed to Middle Cerebral Artery Occlusion","volume":"50","author":"Bieber","year":"2019","journal-title":"Stroke"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2682","DOI":"10.1161\/hs1101.098367","article-title":"Intravenous Administration of Human Umbilical Cord Blood Reduces Behavioral Deficits After Stroke in Rats","volume":"32","author":"Chen","year":"2001","journal-title":"Stroke"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1080\/1061186X.2017.1419360","article-title":"Lipid-coated calcium phosphate nanoparticle and beyond: A versatile platform for drug delivery","volume":"26","author":"Huang","year":"2018","journal-title":"J. Drug Target."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"730121","DOI":"10.1155\/2015\/730121","article-title":"Resveratrol Protects PC12 Cell against 6-OHDA Damage via CXCR4 Signaling Pathway","volume":"2015","author":"Zhang","year":"2015","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.reth.2020.03.001","article-title":"Dexmedetomidine protects PC12 cells from ropivacaine injury through miR-381\/LRRC4 \/SDF-1\/CXCR4 signaling pathway","volume":"14","author":"Xue","year":"2020","journal-title":"Regen. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Khan, H., Pan, J.J., Li, Y., Zhang, Z., and Yang, G.Y. (2021). Native and Bioengineered Exosomes for Ischemic Stroke Therapy. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.619565"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7923","DOI":"10.2147\/IJN.S444582","article-title":"Engineered Exosome for Drug Delivery: Recent Development and Clinical Applications","volume":"18","author":"Tian","year":"2023","journal-title":"Int. J. Nanomed."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Cheng, X., Wang, H., Zhang, X., Zhao, S., Zhou, Z., Mu, X., Zhao, C., and Teng, W. (2017). The Role of SDF-1\/CXCR4\/CXCR7 in Neuronal Regeneration after Cerebral Ischemia. Front. Neurosci., 11.","DOI":"10.3389\/fnins.2017.00590"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"111464","DOI":"10.1016\/j.cellsig.2024.111464","article-title":"Enriched environment enhances angiogenesis in ischemic stroke through SDF-1\/CXCR4\/AKT\/mTOR pathway","volume":"124","author":"Zhang","year":"2024","journal-title":"Cell Signal"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/10\/1357\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T04:30:27Z","timestamp":1761193827000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/10\/1357"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,21]]},"references-count":28,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["pharmaceutics17101357"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics17101357","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,21]]}}}