{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:09:46Z","timestamp":1789567786991,"version":"build-2803163510"},"reference-count":60,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004242","name":"Princess Nourah bint Abdulrahman University","doi-asserted-by":"crossref","award":["PNURSP2026R5"],"award-info":[{"award-number":["PNURSP2026R5"]}],"id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Plant-derived bioactives offer pharmacological potential but are often limited by poor delivery and selectivity. The Pulicaria crispa dichloromethane fraction (DCMF) shows potent but non-selective antiproliferative activity. This study aimed to engineer a functional nanoformulation using a MIL-53(Fe) metal\u2013organic framework (MOF) to achieve sustained release and improve in vitro potency and selectivity against colorectal cancer cells. Methods: DCMF was phytochemically profiled by GC-MS. A DCMF@MIL-53(Fe) nanocomposite was synthesized and characterized for particle size, zeta potential, and entrapment efficiency. In vitro release kinetics were evaluated. Anticancer activity and selectivity were assessed in HCT-116 cells. Mechanistic studies included cell-cycle analysis, cell-death assays, and molecular docking. Results: Tomentosin was identified as the predominant constituent (28.82%). The nanocomposite displayed suitable physicochemical properties (mean size: 218 nm; entrapment efficiency: 83.6%) and a clear transition from burst to sustained drug release over 48 h. Nanoencapsulation resulted in a 53-fold increase in cytotoxic potency, calculated on a DCMF-equivalent basis (IC50 = 0.40 \u00b5g\/mL), compared with free DCMF (IC50 = 21.51 \u00b5g\/mL), along with a modest improvement in selectivity. Enhanced activity was associated with G0\/G1 cell cycle arrest and a shift toward necrotic, non-apoptotic cell death. Docking of the predominant constituent, tomentosin, supported plausible interactions with CDK4\/Cyclin D3 and the MDM2\u2013p53 axis, providing structural context for G1\/S checkpoint disruption. Conclusions: MIL-53(Fe) nanoencapsulation converted a non-selective plant extract into a sustained-release formulation with improved in vitro efficacy and selectivity. These findings provide proof-of-concept that rational nano-delivery strategies can mitigate key pharmaceutical limitations of plant-derived fractions and enhance the anticancer potential of traditional medicinal resources.<\/jats:p>","DOI":"10.3390\/pharmaceutics18020227","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T09:15:12Z","timestamp":1770801312000},"page":"227","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Nanoencapsulation of Tomentosin-Rich Pulicaria crispa Fraction in MIL-53(Fe) Improves the Release Profile and In Vitro Anti-Colorectal Cancer Activity"],"prefix":"10.3390","volume":"18","author":[{"given":"Fatma","family":"Abo-Elghiet","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy and Medicinal Plants, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr City, Cairo 11884, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9898-7866","authenticated-orcid":false,"given":"George M.","family":"Hakeem","sequence":"additional","affiliation":[{"name":"Faculty of Biotechnology, October University for Modern Sciences and Arts (MSA University), 6 October City 12566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2274-2016","authenticated-orcid":false,"given":"Rehab","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Beni-Suef University, Beni-Suef 62528, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8235-5715","authenticated-orcid":false,"given":"Mona H.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Medicinal Chemistry and Drug Design, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr City, Cairo 11884, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamies B.","family":"Nabil","sequence":"additional","affiliation":[{"name":"Department of Medical Science, Faculty of Dentistry, the British University in Egypt, Cairo 11837, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zienab E.","family":"Eldin","sequence":"additional","affiliation":[{"name":"Department of Materials Science and Nanotechnology, Faculty of Postgraduate Studies for Advanced Sciences (PSAS), Beni-Suef University, Beni-Suef 62511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha B.","family":"Abd Elhaleem","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, Beni-Suef University, Beni-Suef 62528, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah I.","family":"Othman","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3189-8063","authenticated-orcid":false,"given":"Nourhan","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Science, Cairo University, Giza 12613, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9834-1289","authenticated-orcid":false,"given":"Emad M.","family":"Elzayat","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Science, Cairo University, Giza 12613, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA A Cancer J. 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