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To overcome this challenge, a combination therapy is developed comprising a novel ciprofloxacin derivative\u2010loaded PEGylated polymeric nanoparticles (CIP2b\u2010NPs) and paclitaxel (PTX) against human type\u2010II endometrial cancer (Hec50co with loss of function p53). Cytotoxicity studies reveal strong synergy between CIP2b and PTX against Hec50co, and this is associated with a significant reduction in the IC<jats:sub>50<\/jats:sub> of PTX and increased G2\/M arrest. Upon formulation of CIP2b into PEGylated polymeric nanoparticles, tumor accumulation of CIP2b is significantly improved compared to its soluble counterpart; thus, enhancing the overall antitumor activity of CIP2b when co\u2010administered with PTX. In addition, the co\u2010delivery of CIP2b\u2010NPs with paclitaxel results in a significant reduction in tumor progression. Histological examination of vital organs and blood chemistry\u00a0was normal, confirming the absence of any apparent off\u2010target toxicity. Thus, in a mouse model of human endometrial cancer, the combination of CIP2b\u2010NPs and PTX exhibits superior therapeutic activity in targeting human type\u2010II endometrial cancer.<\/jats:p>","DOI":"10.1002\/smll.202302931","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T06:43:41Z","timestamp":1690872221000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Ciprofloxacin Derivative\u2010Loaded Nanoparticles Synergize with Paclitaxel Against Type II Human Endometrial Cancer"],"prefix":"10.1002","author":[{"given":"Youssef W.","family":"Naguib","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences and Experimental Therapeutics College of Pharmacy University of Iowa Iowa City IA 52242 USA"},{"name":"Department of Pharmaceutics Minia University Minia 61519 Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1454-8654","authenticated-orcid":false,"given":"Suhaila O.","family":"Alhaj\u2010Suliman","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Experimental Therapeutics College of Pharmacy University of Iowa Iowa City IA 52242 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9854-502X","authenticated-orcid":false,"given":"Emad I.","family":"Wafa","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Experimental Therapeutics College of Pharmacy University of Iowa Iowa City IA 52242 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjib","family":"Saha","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Experimental Therapeutics College of Pharmacy University of Iowa Iowa City IA 52242 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kareem","family":"Ebeid","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Experimental Therapeutics College of Pharmacy University of Iowa Iowa City IA 52242 USA"},{"name":"Department of Pharmaceutics Minia University Minia 61519 Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamada H. H.","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Faculty of Pharmacy Minia University Minia 61519 Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somaya A.","family":"Abdel\u2010Rahman","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Experimental Therapeutics College of Pharmacy University of Iowa Iowa City IA 52242 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gamal El\u2010Din A.","family":"Abuo\u2010Rahma","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry Faculty of Pharmacy Minia University Minia 61519 Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean M.","family":"Geary","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Experimental Therapeutics College of Pharmacy University of Iowa Iowa City IA 52242 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1923-6633","authenticated-orcid":false,"given":"Aliasger K.","family":"Salem","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Experimental Therapeutics College of Pharmacy University of Iowa Iowa City IA 52242 USA"},{"name":"Holden Comprehensive Cancer Center University of Iowa Hospitals &amp; Clinics Iowa City IA 52242 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,31]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.48.2596"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(13)70591-6"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1514010"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/157015906776359568"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpainsymman.2006.03.013"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.04.0543"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-014-2607-5"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.71.3552"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2015.05.042"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-017-0009-7"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-017-0038-2"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2021.120876"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2016.07.070"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2023.122093"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.112.005660"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-017-8739-0_11"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.64805"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abk3150"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/adtp.202100058"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-012-0958-3"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2009.02.045"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2012.03.046"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2022.114482"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/smll.201403799"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2011.02.037"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2020.06.005"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2010.04.009"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm11030229"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/1061186X.2017.1365878"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2015.01.002"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp4006968"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1177\/0192623315625859"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neo.2015.11.012"},{"key":"e_1_2_8_34_1","first-page":"15","volume":"2","author":"Martin J.","year":"2018","journal-title":"Int. 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