{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T04:17:22Z","timestamp":1788322642609,"version":"build-2803163510"},"reference-count":50,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"British Lung Foundation","award":["RG14-8"],"award-info":[{"award-number":["RG14-8"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Cancer stem cells (CSCs) play a key role in non-small cell lung cancer (NSCLC) chemoresistance and metastasis. In this study, we used two NSCLC cell lines to investigate the regulating effect of hypoxia in the induction and maintenance of CSC traits. Our study demonstrated hypoxia-induced stemness and chemoresistance at levels comparable to those in typical CSC sphere culture. Activation of the NF-\u03baB pathway (by transfection of NF-\u03baB-p65) plays a key role in NSCLC CSCs and chemoresistance. Disulfiram (DS), an anti-alcoholism drug, showed a strong in vitro anti-CSC effect. It blocked cancer cell sphere reformation and clonogenicity, synergistically enhanced the cytotoxicity of four anti-NSCLC drugs (doxorubicin, gemcitabine, oxaliplatin and paclitaxel) and reversed hypoxia-induced resistance. The effect of DS on CSCs is copper-dependent. A very short half-life in the bloodstream is the major limitation for the translation of DS into a cancer treatment. Our team previously developed a poly lactic-co-glycolic acid (PLGA) nanoparticle encapsulated DS (DS-PLGA) with a long half-life in the bloodstream. Intra venous injection of DS-PLGA in combination with the oral application of copper gluconate has strong anticancer efficacy in a metastatic NSCLC mouse model. Further study may be able to translate DS-PLGA into cancer applications.<\/jats:p>","DOI":"10.3390\/biom14121651","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T05:58:27Z","timestamp":1734933507000},"page":"1651","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["PLGA-Nano-Encapsulated Disulfiram Inhibits Cancer Stem Cells and Targets Non-Small Cell Lung Cancer In Vitro and In Vivo"],"prefix":"10.3390","volume":"14","author":[{"given":"Kate","family":"Butcher","sequence":"first","affiliation":[{"name":"Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK"},{"name":"Disulfican Ltd., Wolverhampton WV9 5HD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhipeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sathishkumar","family":"Kurusamy","sequence":"additional","affiliation":[{"name":"Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK"},{"name":"School of Biosciences, Division of Natural Sciences, University of Kent, Canterbury CT2 7NZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6329-8676","authenticated-orcid":false,"given":"Zaixing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK"},{"name":"Department of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of North China University of Science and Technology, Tangshan 063000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Morris","sequence":"additional","affiliation":[{"name":"Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7670-2859","authenticated-orcid":false,"given":"Mohammad","family":"Najlah","sequence":"additional","affiliation":[{"name":"Faculty of Health, Medicine and Social Care, Anglia Ruskin University, Cambridge CB1 1PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"McConville","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences, Ulster University, Coleraine BT52 1SA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinodh","family":"Kannappan","sequence":"additional","affiliation":[{"name":"Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK"},{"name":"Disulfican Ltd., Wolverhampton WV9 5HD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0509-2605","authenticated-orcid":false,"given":"Weiguang","family":"Wang","sequence":"additional","affiliation":[{"name":"Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton WV1 1LY, UK"},{"name":"Disulfican Ltd., Wolverhampton WV9 5HD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,23]]},"reference":[{"key":"ref_1","unstructured":"World Cancer Research Fund International (2024, December 16). 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