{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T01:24:29Z","timestamp":1776389069228,"version":"3.51.2"},"reference-count":25,"publisher":"IOP Publishing","issue":"5","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":23,"URL":"https:\/\/publishingsupport.iopscience.iop.org\/iop-standard\/v1"},{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"tdm","delay-in-days":23,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"}],"funder":[{"name":"Lady Tata Memorial Trust"},{"name":"Department of Biotechnology, Ministry of Science & Technology","award":["BT\/PR39321\/DRUG\/134\/87\/2021"],"award-info":[{"award-number":["BT\/PR39321\/DRUG\/134\/87\/2021"]}]}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["Biomed. Mater."],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Targeting glucocorticoid Receptors (GR) induces gluconeogenesis in cancer cells, potentially disrupting their glycolytic dependency and acidic tumor microenvironment (TME), thereby creating an energetically unfavourable state and reducing drug resistance by impairing the acid reflux mechanism. Based on this rationale, we developed a GR-mediated liposomal co-delivery system, D1XP-p53, carrying the tumor suppressor gene, p53, and the chemotherapeutic drug, paclitaxel, to overcome the limitations of conventional anti-cancer therapies and to assess whether wild-type p53 enhances the anti-cancer activity of paclitaxel against Oral Squamous Cell Carcinoma (OSCC). <jats:italic>In vitro<\/jats:italic> studies demonstrated that D1XP-p53 selectively decreased the viability of OSCC cells and significantly inhibited their migration, invasion, and proliferation. Mechanistic investigations revealed an upregulation of the BAX\/BCL2 ratio when oral cancer cells were treated with D1XP-p53, indicating the activation of intrinsic apoptotic pathways. The efficacy of D1XP-p53 was further validated in 3D spheroid models using MOC2 and FaDu cell lines, where it significantly reduced spheroid-forming ability and upregulated E-cadherin expression, indicating its potential role in enhancing anti-cancer activity and mitigating cellular migration. <jats:italic>In vivo<\/jats:italic> experiments using a murine model of OSCC with MOC2 cells showed a marked reduction in tumor volume in mice treated with D1XP-p53, with minimal systemic toxicity as assessed by H&amp;E staining and biodistribution analysis. Considering the crucial role of TME components such as tumor-associated macrophages, cancer stem cells, and growth factors in tumor progression and metastasis, we further evaluated the impact of our delivery system, D1XP-p53, on these elements. We observed that D1XP-p53 treatment in mice significantly upregulated the M1\/M2 ratios and decreased the <jats:italic>c-myc<\/jats:italic> and <jats:italic>SOX2<\/jats:italic> expression, indicating the potential role of the delivery system in modulating the TME components. These findings collectively demonstrate that the GR-targeted co-delivery system, D1XP-p53, enhances anti-cancer activity and modulates the TME, offering a promising multi-modal treatment against aggressive oral cancer.<\/jats:p>","DOI":"10.1088\/1748-605x\/ae05a3","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T22:48:44Z","timestamp":1757544524000},"page":"055010","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Glucocorticoid receptor-mediated delivery of paclitaxel and anticancer gene p53 for oral cancer therapeutics"],"prefix":"10.1088","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3444-7092","authenticated-orcid":true,"given":"Kalyani","family":"Sakhare","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4237-5834","authenticated-orcid":true,"given":"Dwaipayan","family":"Bhattacharya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4945-0030","authenticated-orcid":false,"given":"Chhavi","family":"Dhiman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8029-1695","authenticated-orcid":false,"given":"Priyanka","family":"Erukulla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8986-4750","authenticated-orcid":true,"given":"Srija","family":"Bhattacharya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3598-5073","authenticated-orcid":false,"given":"Aasia","family":"Ansari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0641-0257","authenticated-orcid":true,"given":"Piyush","family":"Khandelia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3576-8824","authenticated-orcid":false,"given":"Anjaneyulu","family":"Eanti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2336-6294","authenticated-orcid":true,"given":"Rajkumar","family":"Banerjee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5198-2495","authenticated-orcid":true,"given":"Kumar Pranav","family":"Narayan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"266","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"bmmae05a3bib1","doi-asserted-by":"publisher","DOI":"10.1088\/1748-605X\/ad2407","type":"journal-article","article-title":"Steroid hormone receptor based gene delivery systems as potential oral cancer therapeutics","volume":"19","author":"Bhattacharya","year":"2024","journal-title":"Biomed. Mater."},{"key":"bmmae05a3bib2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nano.2021.102371","type":"journal-article","article-title":"The prospects of nanotherapeutic approaches for targeting tumor-associated macrophages in oral cancer","volume":"34","author":"Bhattacharya","year":"2021","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"bmmae05a3bib3","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1007\/978-3-319-26666-4_12","type":"book","article-title":"Isolation of mouse and human tumor-associated macrophages","author":"Cassetta","year":"2016"},{"key":"bmmae05a3bib4","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1038\/s41392-020-00235-2","type":"journal-article","article-title":"Regulation of cancer cell metabolism: oncogenic MYC in the driver\u2019s seat","volume":"5","author":"Dong","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"bmmae05a3bib5","doi-asserted-by":"publisher","first-page":"3555","DOI":"10.1039\/C9NA00056A","type":"journal-article","article-title":"Dual targeting of folate receptor-expressing glioma tumor-associated macrophages and epithelial cells in the brain using a carbon nanosphere\u2013cationic folate nanoconjugate","volume":"1","author":"Elechalawar","year":"2019","journal-title":"Nanoscale Adv."},{"key":"bmmae05a3bib6","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/1756-8722-3-8","type":"journal-article","article-title":"From basic research to clinical development of MEK1\/2 inhibitors for cancer therapy","volume":"3","author":"Fr\u00e9min","year":"2010","journal-title":"J. Hematol. Oncol."},{"key":"bmmae05a3bib7","doi-asserted-by":"publisher","first-page":"2439","DOI":"10.3892\/ijo.2014.2655","type":"journal-article","article-title":"Paclitaxel in combination with cetuximab exerts antitumor effect by suppressing NF-\u03baB activity in human oral squamous cell carcinoma cell lines","volume":"45","author":"Harada","year":"2014","journal-title":"Int. J. Oncol."},{"key":"bmmae05a3bib8","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1158\/0008-5472.CAN-11-1831","type":"journal-article","article-title":"ERK1\/2 regulation of CD44 modulates oral cancer aggressiveness","volume":"72","author":"Judd","year":"2012","journal-title":"Cancer Res."},{"key":"bmmae05a3bib9","doi-asserted-by":"publisher","first-page":"2639","DOI":"10.1038\/s41598-019-38915-x","type":"journal-article","article-title":"Validation of size estimation of nanoparticle tracking analysis on polydisperse macromolecule assembly","volume":"9","author":"Kim","year":"2019","journal-title":"Sci. Rep."},{"key":"bmmae05a3bib10","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2022.106012","type":"journal-article","article-title":"The mouse oral carcinoma (MOC) model: a 10-year retrospective on model development and head and neck cancer investigations","volume":"132","author":"Kono","year":"2022","journal-title":"Oral Oncol."},{"key":"bmmae05a3bib11","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1002\/ddr.21758","type":"journal-article","article-title":"Kunjiappan S et al 2021 Surface receptor-mediated targeted drug delivery systems for enhanced cancer treatment: a state-of-the-art review","volume":"82","journal-title":"Drug Dev. Res."},{"key":"bmmae05a3bib12","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1007\/s11626-021-00591-5","type":"journal-article","article-title":"Agarose-based spheroid culture enhanced stemness and promoted odontogenic differentiation potential of human dental follicle cells in vitro","volume":"57","author":"Li","year":"2021","journal-title":"Vitro Cell Dev. Biol. Animal"},{"key":"bmmae05a3bib13","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202307263","type":"journal-article","article-title":"Dendritic nanomedicine with boronate bonds for augmented chemo-immunotherapy via synergistic modulation of tumor immune microenvironment","volume":"36","author":"Li","year":"2024","journal-title":"Adv. Mater."},{"key":"bmmae05a3bib14","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmcr.2024.102004","type":"journal-article","article-title":"Paclitaxel-induced acute fibrinous and organizing pneumonitis in early breast cancer: a case report","volume":"48","author":"Limpawittayakul","year":"2024","journal-title":"Respir. Med. Case Rep."},{"key":"bmmae05a3bib15","doi-asserted-by":"publisher","first-page":"1548","DOI":"10.1002\/ijc.33352","type":"journal-article","article-title":"Epithelial-to-mesenchymal transition in oral squamous cell carcinoma: challenges and opportunities","volume":"148","author":"Ling","year":"2021","journal-title":"Int. J. Cancer"},{"key":"bmmae05a3bib16","doi-asserted-by":"publisher","first-page":"2507","DOI":"10.1021\/acs.molpharmaceut.6b00230","type":"journal-article","article-title":"Glucocorticoid receptor-targeted liposomal codelivery of lipophilic drug and anti-Hsp90 gene: strategy to induce drug-sensitivity, EMT-reversal, and reduced malignancy in aggressive tumors","volume":"13","author":"Mondal","year":"2016","journal-title":"Mol. Pharm."},{"key":"bmmae05a3bib17","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1038\/mt.2009.4","type":"journal-article","article-title":"Selective cancer targeting via aberrant behavior of cancer cell-associated glucocorticoid receptor","volume":"17","author":"Mukherjee","year":"2009","journal-title":"Mol. Ther."},{"key":"bmmae05a3bib18","doi-asserted-by":"publisher","first-page":"2873","DOI":"10.1158\/1078-0432.CCR-14-0205","type":"journal-article","article-title":"A surprising cross-species conservation in the genomic landscape of mouse and human oral cancer identifies a transcriptional signature predicting metastatic disease","volume":"20","author":"Onken","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"bmmae05a3bib19","first-page":"349","type":"journal-article","article-title":"Status of the p53 tumor suppressor gene in human squamous carcinoma cell lines","volume":"4","author":"Reiss","year":"1992","journal-title":"Oncol. Research."},{"key":"bmmae05a3bib20","doi-asserted-by":"publisher","first-page":"286","DOI":"10.3389\/fphar.2015.00286","type":"journal-article","article-title":"Advances and challenges of liposome assisted drug delivery","volume":"6","author":"Sercombe","year":"2015","journal-title":"Front. Pharmacol."},{"key":"bmmae05a3bib21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1615\/CritRevOncog.2023046835","type":"journal-article","article-title":"Conventional therapies of oral cancers: highlights on chemotherapeutic agents and radiotherapy, their adverse effects, and the cost burden of conventional Therapies","volume":"28","author":"Shah","year":"2023","journal-title":"Crit. Rev. Oncog."},{"key":"bmmae05a3bib22","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.788755","type":"journal-article","article-title":"Transforming growth factor-beta-regulated LncRNA-MUF promotes invasion by modulating the miR-34a Snail1 axis in glioblastoma multiforme","volume":"11","author":"Shree","year":"2022","journal-title":"Front. Oncol."},{"key":"bmmae05a3bib23","doi-asserted-by":"publisher","first-page":"149","DOI":"10.3389\/fphar.2012.00149","type":"journal-article","article-title":"Recurrent oral cancer: current and emerging therapeutic approaches","volume":"3","author":"Silva","year":"2012","journal-title":"Front. Pharmacol."},{"key":"bmmae05a3bib24","doi-asserted-by":"publisher","first-page":"718","DOI":"10.2214\/ajr.176.3.1760718","type":"journal-article","article-title":"Paclitaxel-Induced Hypersensitivity Pneumonitis","volume":"176","author":"Wong","year":"2001","journal-title":"Am. J. Roentgenol."},{"key":"bmmae05a3bib25","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202401304","type":"journal-article","article-title":"Dendritic polymer-based nanomedicines remodel the tumor stroma: improve drug penetration and enhance antitumor immune response","volume":"36","author":"Zhang","year":"2024","journal-title":"Adv. Mater."}],"container-title":["Biomedical Materials"],"original-title":[],"link":[{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1748-605X\/ae05a3","content-type":"text\/html","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1748-605X\/ae05a3\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1748-605X\/ae05a3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1748-605X\/ae05a3\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1748-605X\/ae05a3\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1748-605X\/ae05a3\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1748-605X\/ae05a3\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1748-605X\/ae05a3\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T09:41:05Z","timestamp":1758706865000},"score":1,"resource":{"primary":{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1748-605X\/ae05a3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,1]]},"references-count":25,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,9,24]]},"published-print":{"date-parts":[[2025,9,1]]}},"URL":"https:\/\/doi.org\/10.1088\/1748-605x\/ae05a3","relation":{},"ISSN":["1748-6041","1748-605X"],"issn-type":[{"value":"1748-6041","type":"print"},{"value":"1748-605X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,1]]},"assertion":[{"value":"Glucocorticoid receptor-mediated delivery of paclitaxel and anticancer gene p53 for oral cancer therapeutics","name":"article_title","label":"Article Title"},{"value":"Biomedical Materials","name":"journal_title","label":"Journal Title"},{"value":"paper","name":"article_type","label":"Article Type"},{"value":"\u00a9 2025 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.","name":"copyright_information","label":"Copyright Information"},{"value":"2025-02-12","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2025-09-10","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2025-09-24","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}