{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T10:17:30Z","timestamp":1771064250798,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T00:00:00Z","timestamp":1644451200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["FCT program contract IF\/01459\/2015"],"award-info":[{"award-number":["FCT program contract IF\/01459\/2015"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/148406\/2019 and 2020.08310.BD"],"award-info":[{"award-number":["SFRH\/BD\/148406\/2019 and 2020.08310.BD"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>The conception of novel anticancer delivery systems and the combination of chronobiology with nanotechnology may provide a powerful tool to optimize cancer therapy. In this work, polyethylenimine (PEI) has been used to complex p53 encoded plasmid DNA (pDNA), and the anticancer drug methotrexate (MTX) has also been loaded into the vectors. To investigate the influence of circadian clock on drug\/gene delivery efficiency, HeLa, C33A and fibroblast cells have been transfected with developed PEI\/pDNA\/MTX delivery vectors at six different time points. Phenomena as the cellular uptake\/internalization, drug\/gene delivery and p53 protein production have been evaluated. The cell-associated MTX fluorescence have been monitored, and p53 protein levels quantified. In HeLa and C33A cancer cells, significant levels of MTX were found for T8 and T12. For these time points, a high amount of p53 protein was quantified. Confocal microscopy images showed successful HeLa cell\u2019s uptake of PEI\/pDNA\/MTX particles, at T8. In comparison, poor levels of MTX and p53 protein were found in fibroblasts; nevertheless, results indicated rhythmicity. Data demonstrate the influence of circadian rhythm on both cancer-cells targeting ability and transfection performance of PEI\/pDNA\/MTX carriers and seemed to provide the optimum time for drug\/gene delivery. This report adds a great contribution to the field of cancer chronobiology, highlighting the relationship between circadian rhythm and nanodelivery systems, and charting the path for further research on a, yet, poorly explored but promising topic.<\/jats:p>","DOI":"10.3390\/polym14040681","type":"journal-article","created":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T02:35:51Z","timestamp":1644546951000},"page":"681","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Influence of Circadian Rhythm on Cancer Cells Targeting and Transfection Efficiency of a Polycation-Drug\/Gene Delivery Vector"],"prefix":"10.3390","volume":"14","author":[{"given":"T\u00e2nia","family":"Albuquerque","sequence":"first","affiliation":[{"name":"CICS-UBI-Health Sciences Research Centre, Universidade da Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"}]},{"given":"Ana R.","family":"Neves","sequence":"additional","affiliation":[{"name":"CICS-UBI-Health Sciences Research Centre, Universidade da Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"}]},{"given":"Telma","family":"Quintela","sequence":"additional","affiliation":[{"name":"CICS-UBI-Health Sciences Research Centre, Universidade da Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"},{"name":"UDI-IPG-Unidade de Investiga\u00e7\u00e3o para o Desenvolvimento do Interior, Instituto Polit\u00e9cnico da Guarda, 6300-559 Guarda, Portugal"}]},{"given":"Diana","family":"Costa","sequence":"additional","affiliation":[{"name":"CICS-UBI-Health Sciences Research Centre, Universidade da Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.sleep.2017.04.008","article-title":"Evolution of circadian rhythms: From bacteria to human","volume":"35","author":"Bhadra","year":"2017","journal-title":"Sleep Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/nrg.2016.150","article-title":"Transcriptional architecture of the mammalian circadian clock","volume":"18","author":"Takahashi","year":"2017","journal-title":"Nat. Rev. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1038\/sj.ijo.0803778","article-title":"Association between polymorphisms in the Clock gene, obesity and the metabolic syndrome in man","volume":"32","author":"Scott","year":"2008","journal-title":"Int. J. 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