{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:05:49Z","timestamp":1790345149475,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T00:00:00Z","timestamp":1766793600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T00:00:00Z","timestamp":1766793600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371967"],"award-info":[{"award-number":["82371967"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Clinical adoption of nanodrugs for pediatric cancer is hindered by age\u2010associated disparities, with unclear mechanisms limiting nanotherapeutics for childhood solid tumors. Here, we originally find that the in vivo biodistribution of nanocarriers shows marked age differences: juvenile tumor\u2010bearing mice have worse off\u2010target distribution than adults, due to vigorous neovascular proliferation in normal tissues and heightened macrophage phagocytosis in liver and spleen. To address this challenge, an ultrasound\u2010activated liposomal prodrug (CSCPTL) is designed to overcome age\u2010related disparities in off\u2010target distribution. CSCPTL is composed of a camptothecin\u2010lipid prodrug conjugate (SCPT) containing the reactive oxygen species (ROS)\u2010cleavable thioketal linker, a sonosensitizer (chlorin e6, Ce6)\u2010modified lipid, and other commercially available lipids. Upon intravenous injection, the inactive SCPT exerts minimal pharmacological effects on healthy cells. Conversely, once CSCPTL reaches the tumor site and is internalized by cancer cells, ultrasound irradiation activates Ce6 rapidly to generate massive ROS, which cleaves the thioketal linker to release active camptothecin to induce cell apoptosis. CSCPTL showed potent antitumor efficacy in juvenile hepatoblastoma models, showing superior biocompatibility and no side effects, compared with clinically approved nanodrugs such as Abraxane, Doxil, and Onivyde. This study highlights age\u2010related off\u2010target issues and offers a promising ultrasound\u2010controlled strategy for childhood solid tumors.<\/jats:p>","DOI":"10.1002\/advs.202513148","type":"journal-article","created":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T09:50:28Z","timestamp":1766829028000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Ultrasound\u2010Boosted Liposomal Prodrug Overcomes Age\u2010Associated Biodistribution Disparity in Pediatric Solid Tumor Therapy"],"prefix":"10.1002","volume":"13","author":[{"given":"Danfei","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pediatrics The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine) Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjun","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Second Affiliated Hospital of Zhejiang University School of Medicine Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine) Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jue","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine) Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobo","family":"Xuan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine) Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifang","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine) Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingdong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Second Affiliated Hospital of Zhejiang University School of Medicine Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7104-9915","authenticated-orcid":false,"given":"Zhuxian","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Chemical and Biological Engineering Zhejiang Key Laboratory of Smart Biomaterials and Key Laboratory of Biomass Chemical Engineering of Ministry of Education Zhejiang University  Hangzhou China"},{"name":"Department of Ultrasound in Medicine The Second Affiliated Hospital of Zhejiang University School of Medicine Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guowei","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Chemical and Biological Engineering Zhejiang Key Laboratory of Smart Biomaterials and Key Laboratory of Biomass Chemical Engineering of Ministry of Education Zhejiang University  Hangzhou China"},{"name":"Department of Ultrasound in Medicine The Second Affiliated Hospital of Zhejiang University School of Medicine Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.01367"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-23-0451"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canep.2020.101733"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw4892"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30761-7"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cai2.66"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-0090-8"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41578-021-00315-x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-024-01754-7"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/cbe.3c00023"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/cbe.4c00122"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-023-01502-3"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-024-02020-z"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2019.08.008"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-7568(21)00179-3"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2011.03.024"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1166\/jbt.2017.1645"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1159\/000081337"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nano.2021.102366"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-025-01877-5"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-023-01498-w"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.0c00779"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202411092"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2025.04.038"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.31155"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sempedsurg.2022.151233"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.17998\/jlc.2022.02.24"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2012.03.020"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41578-024-00766-y"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44222-024-00154-9"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/EXP.20220045"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-08401-0"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2023.115178"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adp7206"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202004172"},{"key":"e_1_2_10_37_1","article-title":"Unraveling the Plasma Protein Corona by Ultrasonic Cavitation Augments Active\u2010Transporting of Liposome in Solid Tumor","volume":"35","author":"Wang G.","year":"2023","journal-title":"Advanced Materials"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1039\/c2an16141a"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/nn305791q"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201200454"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2006.03.018"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.05.004"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41578-021-00385-x"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.22377\/ajp.v19i01.6071"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202513148","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202513148","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202513148","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:06:19Z","timestamp":1788869179000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202513148"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,27]]},"references-count":43,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/advs.202513148"],"URL":"https:\/\/doi.org\/10.1002\/advs.202513148","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,27]]},"assertion":[{"value":"2025-07-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13148"}}