{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T14:29:16Z","timestamp":1788791356846,"version":"build-2803163510"},"reference-count":92,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>MGN-3 (Biobran), a denatured hemicellulose compound derived from rice bran, possesses potent immunomodulatory and antitumor activity; however, its clinical application is constrained by non-specific tissue distribution, rapid systemic elimination, and poor cellular uptake. To overcome these pharmacological limitations, we engineered MGN-3-loaded lipid nanoparticles (MGN-3.LNPs) formulated with bioactive cinnamon and avocado oils to optimize targeted drug delivery against solid carcinoma. Mice bearing subcutaneous Ehrlich Ascites Carcinoma (EAC) solid tumors received free MGN-3, plain lipid nanoparticles (plain LNPs), or MGN-3.LNPs three times weekly from day 8 to day 26 post-inoculation. The administration of MGN-3.LNPs achieved superior tumor volume suppression (95.00%) compared to free MGN-3 (69.00%) and plain LNPs (63.00%) (p &lt; 0.0001). Mechanistically, MGN-3.LNPs effectively inhibited cancer cell proliferation by suppressing Ki-67 expression while promoting expression shifts that strongly suggest the engagement of mitochondrial-mediated apoptotic signaling, including upregulation of tumor protein p53, Caspase-3, Caspase-9, poly(ADP-ribose) polymerase (PARP), and cytosolic cytochrome c (Cyt c), alongside an elevated Bax\/Bcl-2 ratio and reduced 8-hydroxy-2\u2032-deoxyguanosine (8-OHdG) levels. Flow cytometric analysis confirmed that MGN-3.LNPs induced marked G0\/G1 cell cycle arrest and promoted sub-G1 apoptotic cell accumulation, which was corroborated by Annexin V\/propidium iodide (Annexin V\/PI) staining and semiquantitative histopathological evaluation. Furthermore, MGN-3.LNPs downregulated the gene expression of proinflammatory cytokines tumor necrosis factor-alpha (TNF-\u03b1) and interleukin-6 (IL-6) while restoring redox homeostasis in tumor tissues. Overall, lipidic nanoencapsulation significantly enhances the therapeutic efficacy of MGN-3 against solid tumors through superior nanoscale tissue penetration, prolonged retention, and synergistic lipid\u2013drug bioactivity.<\/jats:p>","DOI":"10.3390\/ijms27177953","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:53:28Z","timestamp":1788789208000},"page":"7953","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhancement of Anti-Neoplastic Effects of MGN-3\/Biobran Against Solid Ehrlich Carcinoma-Bearing Mice via Lipidic Nanoparticle Based Targeted Drug Delivery System"],"prefix":"10.3390","volume":"27","author":[{"given":"Zeinab A.","family":"Alerksosy","sequence":"first","affiliation":[{"name":"Zoology Department, Faculty of Science, Mansoura University, Mansoura 35516, Dakahlia Governorate, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Mamdooh H.","family":"Ghoneum","sequence":"additional","affiliation":[{"name":"Department of Surgery, Charles Drew University of Medicine and Science, Los Angeles, CA 90059, USA"},{"name":"Department of Surgery, University of California, Los Angeles, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4013-4698","authenticated-orcid":false,"given":"Mai","family":"Alaa El-Dein","sequence":"additional","affiliation":[{"name":"Zoology Department, Faculty of Science, Mansoura University, Mansoura 35516, Dakahlia Governorate, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8159-8929","authenticated-orcid":false,"given":"Sarah","family":"Yahia","sequence":"additional","affiliation":[{"name":"Nanomedicine Research Labs, Center for Materials Science (CMS), Zewail City of Science and Technology, 6th October City 12578, Giza, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8179-437X","authenticated-orcid":false,"given":"Ibrahim M.","family":"El-Sherbiny","sequence":"additional","affiliation":[{"name":"Nanomedicine Research Labs, Center for Materials Science (CMS), Zewail City of Science and Technology, 6th October City 12578, Giza, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9787-9872","authenticated-orcid":false,"given":"Nariman K.","family":"Badr El-Din","sequence":"additional","affiliation":[{"name":"Zoology Department, Faculty of Science, Mansoura University, Mansoura 35516, Dakahlia Governorate, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,7]]},"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 Cancer J. 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