{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:18:07Z","timestamp":1792811887819,"version":"4.5.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T00:00:00Z","timestamp":1782604800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":78,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"The Science and Technology Research Project of Henan Province","award":["252102310336"],"award-info":[{"award-number":["252102310336"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Nanobiotechnol"],"DOI":"10.1186\/s12951-026-04748-w","type":"journal-article","created":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T16:54:48Z","timestamp":1782665688000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A pH\u2011responsive hydrogel delivering ISOC1 modRNA attenuates disc degeneration by promoting BIRC6\u2011mediated MYC degradation and inhibiting SBSN expression"],"prefix":"10.1186","volume":"24","author":[{"given":"Kun","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanzheng","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guowang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Lian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,28]]},"reference":[{"key":"4748_CR1","unstructured":"Global regional. and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990\u20132017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet (London, England). 2018;392(10159):1789\u2009\u2013\u2009858."},{"issue":"4","key":"4748_CR2","doi-asserted-by":"publisher","first-page":"e70011","DOI":"10.1002\/jsp2.70011","volume":"7","author":"H Sun","year":"2024","unstructured":"Sun H, Guo J, Xiong Z, Zhuang Y, Ning X, Liu M. Targeting nucleus pulposus cell death in the treatment of intervertebral disc degeneration. JOR spine. 2024;7(4):e70011.","journal-title":"JOR spine"},{"key":"4748_CR3","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1016\/j.bioactmat.2025.02.036","volume":"48","author":"G Yang","year":"2025","unstructured":"Yang G, Dong C, Wu Z, Wu P, Yang C, Li L, et al. Single-cell RNA sequencing-guided engineering of mitochondrial therapies for intervertebral disc degeneration by regulating mtDNA\/SPARC-STING signaling. Bioactive Mater. 2025;48:564\u201382.","journal-title":"Bioactive Mater"},{"key":"4748_CR4","doi-asserted-by":"publisher","first-page":"156234","DOI":"10.1016\/j.metabol.2025.156234","volume":"168","author":"Y Liao","year":"2025","unstructured":"Liao Y, Niu L, Ling J, Cui Y, Huang Z, Xu J, et al. Turning sour into sweet: Lactylation modification as a promising target in cardiovascular health. Metab Clin Exp. 2025;168:156234.","journal-title":"Metab Clin Exp"},{"issue":"1","key":"4748_CR5","doi-asserted-by":"publisher","first-page":"174","DOI":"10.4149\/neo_2021_210815N1157","volume":"69","author":"J Xiang","year":"2022","unstructured":"Xiang J, Gao XQ, Chen XL, Lu YY. ISOC1 is a novel potential tumor suppressor in hepatocellular carcinoma. Neoplasma. 2022;69(1):174\u201382.","journal-title":"Neoplasma"},{"issue":"8","key":"4748_CR6","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1093\/carcin\/bgz188","volume":"41","author":"B Gao","year":"2020","unstructured":"Gao B, Zhao L, Wang F, Bai H, Li J, Li M, et al. Knockdown of ISOC1 inhibits the proliferation and migration and induces the apoptosis of colon cancer cells through the AKT\/GSK-3\u03b2 pathway. Carcinogenesis. 2020;41(8):1123\u201333.","journal-title":"Carcinogenesis"},{"key":"4748_CR7","doi-asserted-by":"crossref","unstructured":"Lin X, Zhao Q, Fu B, Xiong Y, Zhang S, Xu S et al. ISOC1 Modulates Inflammatory Responses in Macrophages through the AKT1\/PEX11B\/Peroxisome Pathway. Molecules. 2022;27(18): 5896.","DOI":"10.3390\/molecules27185896"},{"issue":"1","key":"4748_CR8","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1038\/s42003-024-06000-3","volume":"7","author":"Y Zhang","year":"2024","unstructured":"Zhang Y, Huang Z, Han W, Wu J, Li S, Qin T, et al. Glutamine suppresses senescence and promotes autophagy through glycolysis inhibition-mediated AMPK\u03b1 lactylation in intervertebral disc degeneration. Commun biology. 2024;7(1):325.","journal-title":"Commun biology"},{"key":"4748_CR9","doi-asserted-by":"crossref","unstructured":"Silwal P, Nguyen-Thai AM, Mohammad HA, Wang Y, Robbins PD, Lee JY et al. Cellular Senescence in Intervertebral Disc Aging and Degeneration: Molecular Mechanisms and Potential Therapeutic Opportunities. Biomolecules. 2023;13(4):686.","DOI":"10.3390\/biom13040686"},{"key":"4748_CR10","doi-asserted-by":"publisher","first-page":"157021","DOI":"10.1016\/j.phymed.2025.157021","volume":"145","author":"JJ Lu","year":"2025","unstructured":"Lu JJ, Zhang QC, Chen YT, Yuan GC, Huang YK, Wu T, et al. Cryptotanshinone attenuates lactate-induced nucleus pulposus cells injury by modulating the STAT3\/SIRT3 signaling axis. Phytomedicine: Int J phytotherapy phytopharmacology. 2025;145:157021.","journal-title":"Phytomedicine: Int J phytotherapy phytopharmacology"},{"issue":"5","key":"4748_CR11","first-page":"2553","volume":"41","author":"W Wang","year":"2018","unstructured":"Wang W, Deng G, Qiu Y, Huang X, Xi Y, Yu J, et al. Transplantation of allogenic nucleus pulposus cells attenuates intervertebral disc degeneration by inhibiting apoptosis and increasing migration. Int J Mol Med. 2018;41(5):2553\u201364.","journal-title":"Int J Mol Med"},{"issue":"1","key":"4748_CR12","doi-asserted-by":"publisher","first-page":"2551517","DOI":"10.1080\/08916934.2025.2551517","volume":"58","author":"DJ Speicher","year":"2025","unstructured":"Speicher DJ, Rose J, McKernan K. Quantification of residual plasmid DNA and SV40 promoter-enhancer sequences in Pfizer\/BioNTech and Moderna modRNA COVID-19 vaccines from Ontario. Can Autoimmun. 2025;58(1):2551517.","journal-title":"Can Autoimmun"},{"issue":"1","key":"4748_CR13","doi-asserted-by":"publisher","first-page":"a014035","DOI":"10.1101\/cshperspect.a014035","volume":"5","author":"KR Chien","year":"2014","unstructured":"Chien KR, Zangi L, Lui KO. Synthetic chemically modified mRNA (modRNA): toward a new technology platform for cardiovascular biology and medicine. Cold Spring Harbor Perspect Med. 2014;5(1):a014035.","journal-title":"Cold Spring Harbor Perspect Med"},{"key":"4748_CR14","first-page":"77","volume":"2573","author":"J Yoo","year":"2022","unstructured":"Yoo J, Zangi L. Optimization of Synthesis of Modified mRNA. Methods in molecular biology. (Clifton NJ). 2022;2573:77\u201387.","journal-title":"(Clifton NJ)"},{"issue":"15","key":"4748_CR15","doi-asserted-by":"publisher","first-page":"7219","DOI":"10.7150\/thno.112077","volume":"15","author":"A Magadum","year":"2025","unstructured":"Magadum A, Mallaredy V, Roy R, Joladarashi D, Thej C, Cheng Z, et al. Phosphoserine aminotransferase 1 promotes serine synthesis pathway and cardiac repair after myocardial infarction. Theranostics. 2025;15(15):7219\u201341.","journal-title":"Theranostics"},{"issue":"3","key":"4748_CR16","doi-asserted-by":"publisher","first-page":"e70250","DOI":"10.1002\/ctm2.70250","volume":"15","author":"K Li","year":"2025","unstructured":"Li K, Luo R, Yu X, Dong W, Hao G, Hu D, et al. Enhanced human adipose-derived stem cells with VEGFA and bFGF mRNA promote stable vascular regeneration and improve cardiac function following myocardial infarction. Clin translational Med. 2025;15(3):e70250.","journal-title":"Clin translational Med"},{"issue":"16","key":"4748_CR17","first-page":"1801664","volume":"6","author":"S Talebian","year":"2019","unstructured":"Talebian S, Mehrali M, Taebnia N, Pennisi CP, Kadumudi FB, Foroughi J, et al. Self-Healing Hydrogels: The Next Paradigm Shift in Tissue Engineering? Adv Sci (Weinheim Baden-Wurttemberg Germany). 2019;6(16):1801664.","journal-title":"Adv Sci (Weinheim Baden-Wurttemberg Germany)"},{"key":"4748_CR18","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.carbpol.2015.12.032","volume":"140","author":"D Zhang","year":"2016","unstructured":"Zhang D, Yu G, Long Z, Yang G, Wang B. Controllable layer-by-layer assembly of PVA and phenylboronic acid-derivatized chitosan. Carbohydr Polym. 2016;140:228\u201332.","journal-title":"Carbohydr Polym"},{"issue":"1","key":"4748_CR19","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/s10495-025-02231-9","volume":"31","author":"K Wang","year":"2026","unstructured":"Wang K, Ji H, Gao J, Wang Z, Gao Y, Lian X, et al. DDIT3 drives nucleus pulposus cell PANoptosis and intervertebral disc degeneration progression. Apoptosis: Int J Program cell death. 2026;31(1):25.","journal-title":"Apoptosis: Int J Program cell death"},{"key":"4748_CR20","doi-asserted-by":"crossref","unstructured":"Hu X, Wang Z, Zhang H, Cui P, Li Y, Chen X, et al. Single-cell sequencing: New insights for intervertebral disc degeneration. Volume 165. Biomedicine & pharmacotherapy\u2009=\u2009Biomedecine & pharmacotherapie; 2023. p. 115224.","DOI":"10.1016\/j.biopha.2023.115224"},{"key":"4748_CR21","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.2147\/DDDT.S448807","volume":"18","author":"Y Hu","year":"2024","unstructured":"Hu Y, Yang R, Liu S, Song Z, Wang H. The Emerging Roles of Nanocarrier Drug Delivery System in Treatment of Intervertebral Disc Degeneration-Current Knowledge, Hot Spots, Challenges and Future Perspectives. Drug Des Devel Ther. 2024;18:1007\u201322.","journal-title":"Drug Des Devel Ther"},{"key":"4748_CR22","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.bioactmat.2022.11.006","volume":"23","author":"W Liu","year":"2023","unstructured":"Liu W, Ma Z, Wang Y, Yang J. Multiple nano-drug delivery systems for intervertebral disc degeneration: Current status and future perspectives. Bioactive Mater. 2023;23:274\u201399.","journal-title":"Bioactive Mater"},{"key":"4748_CR23","doi-asserted-by":"publisher","first-page":"1172920","DOI":"10.3389\/fphar.2023.1172920","volume":"14","author":"J Xu","year":"2023","unstructured":"Xu J, Shao T, Lou J, Zhang J, Xia C. Aging, cell senescence, the pathogenesis and targeted therapies of intervertebral disc degeneration. Front Pharmacol. 2023;14:1172920.","journal-title":"Front Pharmacol"},{"key":"4748_CR24","doi-asserted-by":"publisher","first-page":"114066","DOI":"10.1016\/j.jconrel.2025.114066","volume":"386","author":"J Zhang","year":"2025","unstructured":"Zhang J, Li C, Liu H, Wang Q, Xu AY, Shah K, et al. Hydrogel delivery systems in intervertebral disc degeneration: Current status and future perspectives. J controlled release: official J Controlled Release Soc. 2025;386:114066.","journal-title":"J controlled release: official J Controlled Release Soc"},{"issue":"21","key":"4748_CR25","doi-asserted-by":"publisher","first-page":"e142","DOI":"10.1093\/nar\/gkr695","volume":"39","author":"K Karik\u00f3","year":"2011","unstructured":"Karik\u00f3 K, Muramatsu H, Ludwig J, Weissman D. Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA. Nucleic Acids Res. 2011;39(21):e142.","journal-title":"Nucleic Acids Res"},{"issue":"4","key":"4748_CR26","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1016\/j.ymthe.2018.12.011","volume":"27","author":"AG von Orlandini","year":"2019","unstructured":"von Orlandini AG, Poleganov MA, Rechner C, Plaschke A, Kranz LM, Fesser S, et al. Improving mRNA-Based Therapeutic Gene Delivery by Expression-Augmenting 3\u2019 UTRs Identified by Cellular Library Screening. Mol therapy: J Am Soc Gene Therapy. 2019;27(4):824\u201336.","journal-title":"Mol therapy: J Am Soc Gene Therapy"},{"issue":"11","key":"4748_CR27","doi-asserted-by":"publisher","first-page":"1833","DOI":"10.1038\/mt.2008.200","volume":"16","author":"K Karik\u00f3","year":"2008","unstructured":"Karik\u00f3 K, Muramatsu H, Welsh FA, Ludwig J, Kato H, Akira S, et al. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol therapy: J Am Soc Gene Therapy. 2008;16(11):1833\u201340.","journal-title":"Mol therapy: J Am Soc Gene Therapy"},{"issue":"25","key":"4748_CR28","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.1038\/s41388-024-03048-7","volume":"43","author":"S Motomura","year":"2024","unstructured":"Motomura S, Yumimoto K, Tomonaga T, Nakayama KI. CRL2(KLHDC3) and CRL1(Fbxw7) cooperatively mediate c-Myc degradation. Oncogene. 2024;43(25):1917\u201329.","journal-title":"Oncogene"},{"issue":"5","key":"4748_CR29","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1016\/S1097-2765(03)00173-4","volume":"11","author":"SY Kim","year":"2003","unstructured":"Kim SY, Herbst A, Tworkowski KA, Salghetti SE, Tansey WP. Skp2 regulates Myc protein stability and activity. Mol Cell. 2003;11(5):1177\u201388.","journal-title":"Mol Cell"},{"key":"4748_CR30","doi-asserted-by":"crossref","unstructured":"Houri A, Mukudai Y, Abe Y, Watanabe M, Nara M, Miyamoto S et al. Suprabasin enhances the invasion, migration, and angiogenic ability of oral squamous cell carcinoma cells under hypoxic conditions. Oncol Rep. 2023;49(5):83.","DOI":"10.3892\/or.2023.8520"},{"issue":"3","key":"4748_CR31","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.jdermsci.2019.07.009","volume":"95","author":"M Aoshima","year":"2019","unstructured":"Aoshima M, Phadungsaksawasdi P, Nakazawa S, Iwasaki M, Sakabe JI, Umayahara T, et al. Decreased expression of suprabasin induces aberrant differentiation and apoptosis of epidermal keratinocytes: Possible role for atopic dermatitis. J Dermatol Sci. 2019;95(3):107\u201312.","journal-title":"J Dermatol Sci"},{"issue":"1","key":"4748_CR32","doi-asserted-by":"publisher","first-page":"3526","DOI":"10.1038\/s41467-021-23752-2","volume":"12","author":"V Ecker","year":"2021","unstructured":"Ecker V, Stumpf M, Brandmeier L, Neumayer T, Pfeuffer L, Engleitner T, et al. Targeted PI3K\/AKT-hyperactivation induces cell death in chronic lymphocytic leukemia. Nat Commun. 2021;12(1):3526.","journal-title":"Nat Commun"},{"key":"4748_CR33","doi-asserted-by":"publisher","first-page":"156060","DOI":"10.1016\/j.phymed.2024.156060","volume":"135","author":"A \u015eengelen","year":"2024","unstructured":"\u015eengelen A, \u00d6nay-U\u00e7ar E. Rosmarinic acid attenuates glioblastoma cells and spheroids\u2019 growth and EMT\/stem-like state by PTEN\/PI3K\/AKT downregulation and ERK-induced apoptosis. Phytomedicine: Int J phytotherapy phytopharmacology. 2024;135:156060.","journal-title":"Phytomedicine: Int J phytotherapy phytopharmacology"},{"issue":"1","key":"4748_CR34","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1186\/s12967-025-06169-z","volume":"23","author":"L Qiu","year":"2025","unstructured":"Qiu L, Gao Q, Liao Y, Li X, Li C. Targeted inhibition of the PTEN\/PI3K\/AKT pathway by YSV induces cell cycle arrest and apoptosis in oral squamous cell carcinoma. J translational Med. 2025;23(1):145.","journal-title":"J translational Med"},{"issue":"1","key":"4748_CR35","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1038\/s41413-025-00449-6","volume":"13","author":"Z Lin","year":"2025","unstructured":"Lin Z, Lu X, Xu G, Song J, Wang H, Xia X, et al. The mitochondrial E3 ligase MAPL SUMOylates Drp1 to facilitate mitochondrial fission in intervertebral disc degeneration. Bone Res. 2025;13(1):72.","journal-title":"Bone Res"},{"issue":"11","key":"4748_CR36","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1016\/j.joca.2025.08.005","volume":"33","author":"C Zhang","year":"2025","unstructured":"Zhang C, Gao S, Han W, Wu J, Huang Z, Zhang X, et al. L-arginine alleviates intervertebral disc degeneration by suppressing TRIB3\/AKAP1-mediated Drp1 phosphorylation dysregulation and mitochondrial fragmentation. Osteoarthr Cartil. 2025;33(11):1332\u201348.","journal-title":"Osteoarthr Cartil"},{"issue":"5\u20136","key":"4748_CR37","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1007\/s00011-022-01570-6","volume":"71","author":"X Peng","year":"2022","unstructured":"Peng X, Zhang C, Zhou ZM, Wang K, Gao JW, Qian ZY, et al. A20 attenuates pyroptosis and apoptosis in nucleus pulposus cells via promoting mitophagy and stabilizing mitochondrial dynamics. Inflamm research: official J Eur Histamine Res Soc [et al]. 2022;71(5\u20136):695\u2013710.","journal-title":"Inflamm research: official J Eur Histamine Res Soc [et al]"},{"key":"4748_CR38","doi-asserted-by":"crossref","unstructured":"Sun Y, Li X, Yang X, Chen B, Zhang W. Small Extracellular Vesicles Derived from Adipocytes Attenuate Intervertebral Disc Degeneration in Rats by Rejuvenating Senescent Nucleus Pulposus Cells and Endplate Cells by Delivering Exogenous NAMPT. Oxidative medicine and cellular longevity. 2021;2021:9955448.","DOI":"10.1155\/2021\/9955448"},{"issue":"3","key":"4748_CR39","doi-asserted-by":"publisher","first-page":"e12779","DOI":"10.1111\/cpr.12779","volume":"53","author":"L Kang","year":"2020","unstructured":"Kang L, Liu S, Li J, Tian Y, Xue Y, Liu X. The mitochondria-targeted anti-oxidant MitoQ protects against intervertebral disc degeneration by ameliorating mitochondrial dysfunction and redox imbalance. Cell Prolif. 2020;53(3):e12779.","journal-title":"Cell Prolif"}],"container-title":["Journal of Nanobiotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12951-026-04748-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12951-026-04748-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12951-026-04748-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T14:03:47Z","timestamp":1789394627000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12951-026-04748-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,28]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4748"],"URL":"https:\/\/doi.org\/10.1186\/s12951-026-04748-w","relation":{},"ISSN":["1477-3155"],"issn-type":[{"value":"1477-3155","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,28]]},"assertion":[{"value":"5 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All clinical investigations were conducted with approval from the Medical Ethics Committee of Henan Provincial People\u2019s Hospital (No. 2023\u2009\u2212\u2009148) in compliance with the Declaration of Helsinki. The requirement for informed consent was waived for retrospective analysis of anonymized patient data. Animal experiments were performed under protocols approved by the Animal Experimental Ethics Committee of Southeast University (No. 20210907001), in accordance with ARRIVE 2.0 guidelines.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"868"}}