{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T13:10:01Z","timestamp":1793797801291,"version":"4.6.1"},"reference-count":71,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T00:00:00Z","timestamp":1661299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A PEGylated niosomal formulation of cyclophosphamide (Nio-Cyclo-PEG) was prepared using a central composite design and characterized in terms of drug loading, size distribution, and average size. The stability of formulations was also studied at different conditions. In vitro cytotoxicity of drug delivery formulations was assessed on gastric cancer cells using MTT assay. The mechanism of cytotoxicity was studied at the transcriptional level by real-time PCR on Caspase3, Caspase9, CyclinD, CyclinE, MMP-2, and MMP-9 genes, while apoptosis was investigated with flow cytometry. The anti-metastatic property was evaluated using the scratch method. Propidium iodide staining was used to study the cell cycle. The results indicated that the as-designed nanocarrier exhibited a controlled drug release pattern with improved nanoparticle stability. It was found that the living cancer cells treated with Nio-Cyclo-PEG showed a significant decrease in number when compared with the niosomal carrier without PEG (Nio-Cyclo) and free drug (Cyclo). Moreover, the drug-loaded nanocarrier induced planned death (apoptosis) in the cancer cells through the regulation of Caspase3, Caspase9, CyclinD, CyclinE, MMP-9, and MMP-2 gene expression, indicating that the Nio-Cyclo-PEG formulation could significantly inhibit the cell cycle at the sub G1 phase as well as prevent the migration of cancer cells. In conclusion, Nio-Cyclo-PEG as developed in this study could serve as an active-targeting drug delivery nanocarriers for gastric cancer therapy with high efficacy and minimal side effects on healthy tissues\/cells.<\/jats:p>","DOI":"10.3390\/molecules27175418","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T23:48:58Z","timestamp":1661384938000},"page":"5418","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["pH-Responsive PEGylated Niosomal Nanoparticles as an Active-Targeting Cyclophosphamide Delivery System for Gastric Cancer Therapy"],"prefix":"10.3390","volume":"27","author":[{"given":"Farnaz","family":"Khodabakhsh","sequence":"first","affiliation":[{"name":"Department of Genetics and Advanced Medical Technology, Medical Biotechnology Research Center, Faculty of Medicine, AJA University of Medical Sciences, Tehran 1411718541, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahsa","family":"Bourbour","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Alzahra University, Tehran 1993893973, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6987-7885","authenticated-orcid":false,"given":"Mohammad Tavakkoli","family":"Yaraki","sequence":"additional","affiliation":[{"name":"School of Natural Sciences, Macquarie University, Sydney, NSW 2109, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3602-4154","authenticated-orcid":false,"given":"Saina","family":"Bazzazan","sequence":"additional","affiliation":[{"name":"Department of Community Medicine, Mashhad Branch, Islamic Azad University, Mashhad 9187147578, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haleh","family":"Bakhshandeh","sequence":"additional","affiliation":[{"name":"Department of Nanobiotechnology, New Technologies Research Group, Pasteur Institute of Iran, Tehran 1316943551, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0490-4184","authenticated-orcid":false,"given":"Reza","family":"Ahangari Cohan","sequence":"additional","affiliation":[{"name":"Department of Nanobiotechnology, New Technologies Research Group, Pasteur Institute of Iran, Tehran 1316943551, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4003-063X","authenticated-orcid":false,"given":"Yen Nee","family":"Tan","sequence":"additional","affiliation":[{"name":"Faculty of Science, Agriculture and Engineering, Newcastle University, Newcastle Upon Tyne NE1 7RU, UK"},{"name":"Newcastle Research and Innovation Institute, Newcastle University in Singapore, Singapore 609607, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41573-020-0090-8","article-title":"Engineering precision nanoparticles for drug delivery","volume":"20","author":"Mitchell","year":"2020","journal-title":"Nat. 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