{
  "abstract": "Achieving precise, on-demand release of therapeutic agents remains a central challenge in pharmacology and chemical biology. In this work, we reported a modular prodrug release platform that employed low-intensity medical ultrasound (1 MHz, 2.5 W cm–2) to trigger the cleavage of carbamate and thiocarbamate linkers in aqueous media, enabling on-demand release of hydrophilic drug payloads. The linker was designed to couple drug release with the concurrent release of methylene blue (MB), allowing fluorescence measurements to track ultrasound-triggered linker cleavage and cargo release from the same molecular construct. Mechanistic studies including radical probes, EPR spectroscopy, Fenton validation, and intracellular DCFH-DA imaging supported the crucial role of cavitation-generated •OH and O2•– for the cleavage of the linkers. Furthermore, we evaluated payload compatibility using topotecan (TPT), an FDA-approved anticancer drug, and N-acetyl-l-cysteine as representative hydroxyl- and thiol-containing prodrugs, respectively. Ultrasound irradiation triggered TPT release and restored the cytotoxic activity of the masked prodrug in HeLa cells, whereas the nonactivated prodrug maintained >86% MCF-10A cell viability. Ex vivo studies also showed that ultrasound-triggered MB and TPT release remained detectable through porcine tissue barriers of 2.0 cm thickness, enabling controlled drug release with fluorescence-based monitoring and tissue-penetrating delivery.",
  "abstract_shown": true,
  "affiliations": [
    "Henan University of Technology , , ,",
    "Nanyang Technological University , , ,",
    "Fudan University , , ,"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Shiyang Chen"
    },
    {
      "affs": [
        1
      ],
      "name": "Shirui Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Raymond Tio"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaolu Zhu"
    },
    {
      "affs": [
        0
      ],
      "name": "Mengyao Liang"
    },
    {
      "affs": [
        0
      ],
      "name": "Huitao Liu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Teck-Peng Loh",
      "orcid": "0000-0002-2936-337X"
    },
    {
      "affs": [
        0
      ],
      "name": "Peng Chen",
      "orcid": "0000-0002-6252-5772"
    },
    {
      "affs": [
        2
      ],
      "name": "Zhenhua Jia"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4jwh4bqbp2wts.bib",
  "cited_by": 0,
  "doi": "10.1021/jacsau.6c01395",
  "fulltext_url": null,
  "id": "4jwh4bqbp2wts",
  "issns": [
    "2691-3704"
  ],
  "landing_url": "https://pubs.acs.org/jaaucr/article/doi/10.1021/jacsau.6c01395/5462552/On-Demand-Drug-Release-under-Ultrasound",
  "language": null,
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": "https://pubs.acs.org/doi/pdf/10.1021/jacsau.6c01395",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-03",
  "publisher": "American Chemical Society (ACS)",
  "ris": "https://research.draconitic.com/paper/4jwh4bqbp2wts.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T12:20:49Z",
      "native_id": "10.1021/jacsau.6c01395",
      "source": "crossref",
      "url": "https://pubs.acs.org/jaaucr/article/doi/10.1021/jacsau.6c01395/5462552/On-Demand-Drug-Release-under-Ultrasound"
    }
  ],
  "subjects": [
    {
      "field": "chemistry",
      "origin": "issn:2691-3704",
      "subfield": "general"
    }
  ],
  "title": "On-Demand Drug Release under Ultrasound Irradiation",
  "title_text": "On-Demand Drug Release under Ultrasound Irradiation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T00:20:51Z",
  "url": "https://research.draconitic.com/paper/4jwh4bqbp2wts",
  "venue": "JACS Au",
  "versions": []
}