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In this study, we developed carrier-free nano drugs based on 5-fluorouracil (5FU) and cinnamaldehyde (CA) to meet the above goals. Two model drugs were spliced by acetal linkage and ester bond, which could self-assemble into nano drug particles (5FU\u2013CA NPs) with a size of \u223c170\u2009nm. In vitro cell experiments showed 5FU\u2013CA NPs were efficiently internalized by HepG2 cells. They then quickly exerted dual drug activities by the cleavage of acetal and ester bond, resulting in enhanced cell-killing efficacy and apoptosis. Synergistic mechanisms were achieved via the anti-metabolic effects mediated by 5FU\u2013COOH and the oxidative damage induced by CA. In vivo anti-tumor evaluation further indicated that 5FU\u2013CA NPs had higher tumor growth inhibition than 5FU\u2013COOH\/CA mixture (5FU\u2013COOH\u2009+\u2009CA) and exhibited lower systemic toxicity under the same reducing dose of each drug. Overall, this is a successful synergistic anti-tumor attempt through rational self-assembly of drugs with different mechanisms and it can be extrapolated to other agents.<\/jats:p>","DOI":"10.1177\/0885328221989539","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T21:33:13Z","timestamp":1613856793000},"page":"592-604","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["Self-assembled 5-fluorouracil-cinnamaldehyde nanodrugs for greatly improved chemotherapy in vivo"],"prefix":"10.1177","volume":"36","author":[{"given":"Qin","family":"Fang","sequence":"first","affiliation":[{"name":"School of Life Science, Anhui University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Life Science, Anhui University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longshun","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Life Science, Anhui University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanbing","family":"Xue","sequence":"additional","affiliation":[{"name":"School of Life Science, Anhui University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Life Science, Anhui University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Science, Anhui University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2885-5049","authenticated-orcid":false,"given":"Rupei","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Life Science, Anhui University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,2,16]]},"reference":[{"key":"bibr1-0885328221989539","doi-asserted-by":"publisher","DOI":"10.1504\/IJNT.2011.037172"},{"key":"bibr2-0885328221989539","doi-asserted-by":"publisher","DOI":"10.2217\/nnm-2017-0316"},{"key":"bibr3-0885328221989539","doi-asserted-by":"publisher","DOI":"10.1021\/nn900002m"},{"key":"bibr4-0885328221989539","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2016.03.027"},{"key":"bibr5-0885328221989539","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-06-0141"},{"key":"bibr6-0885328221989539","doi-asserted-by":"crossref","unstructured":"Huo D, Jiang X, Hu Y. 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