Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/91044
DC FieldValueLanguage
dc.contributorChinese Mainland Affairs Officeen_US
dc.contributorDepartment of Biomedical Engineeringen_US
dc.creatorChen, Xen_US
dc.creatorFan, Yen_US
dc.creatorSun, Jen_US
dc.creatorZhang, Zen_US
dc.creatorXin, Yen_US
dc.creatorLi, Ken_US
dc.creatorTang, Ken_US
dc.creatorDu, Pen_US
dc.creatorLiu, Yen_US
dc.creatorWang, Gen_US
dc.creatorYang, Men_US
dc.creatorTan, Yen_US
dc.date.accessioned2021-09-09T03:38:28Z-
dc.date.available2021-09-09T03:38:28Z-
dc.identifier.urihttp://hdl.handle.net/10397/91044-
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.subjectCellular stiffnessen_US
dc.subjectCancer stem cellen_US
dc.subjectCellular uptakeen_US
dc.subjectMechanomedicineen_US
dc.subjectNanoparticleen_US
dc.titleNanoparticle-mediated specific elimination of soft cancer stem cells by targeting low cell stiffnessen_US
dc.typeJournal/Magazine Articleen_US
dc.identifier.volume132en_US
dc.identifier.doi10.1016/j.actbio.2021.08.053en_US
dcterms.abstractAs the driving force of tumor progression, cancer stem cells (CSCs) hold much lower cellular stiffness than bulk tumor cells across many cancer types. However, it remains unclear whether low cell stiffness can be harnessed in nanoparticle-based therapeutics for CSC targeting. We report that breast CSCs exhibit much lower stiffness but considerably higher uptake of nitrogen-doped graphene quantum dots (N-GQDs) than bulk tumor cells. Softening/stiffening cells enhances/suppresses nanoparticle uptake through activating/inhibiting clathrin- and caveolae-mediated endocytosis, suggesting that low cell stiffness mediates the elevated uptake in soft CSCs that may lead to the specific elimination. Further, soft CSCs enhance drug release, cellular retention, and nuclear accumulation of drug-loaded N-GQDs by reducing intracellular pH and exocytosis. Remarkably, drug-loaded N-GQDs specifically eliminate soft CSCs both in vitro and in vivo, inhibit tumor but not animal growth, and reduce the tumorigenicity of xenograft cells. Our findings unveil a new mechanism by which low cellular stiffness can be harnessed in nanoparticle-based strategies for specific CSC elimination, opening a new paradigm of cancer mechanomedicine.en_US
dcterms.accessRightsembargoed accessen_US
dcterms.bibliographicCitationActa Biomaterialia, 2021, in press, v. 132, https://doi.org/10.1016/j.actbio.2021.08.053en_US
dcterms.isPartOfActa biomaterialiaen_US
dcterms.issued2021-
dc.identifier.eissn1742-7061en_US
dc.description.validate202109 bchyen_US
dc.description.oaNot applicableen_US
dc.identifier.FolderNumbera1025-n01-
dc.identifier.SubFormID2450-
dc.description.fundingSourceRGCen_US
dc.description.fundingTextRGC: PolyU 252094/17E, C5011-19G, PolyU 15216917 and 15214619en_US
dc.description.pubStatusEarly releaseen_US
dc.date.embargo0000-00-00 (to be updated)en_US
Appears in Collections:Journal/Magazine Article
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Embargo End Date 0000-00-00 (to be updated)
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