{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:56:07Z","timestamp":1760147767929,"version":"build-2065373602"},"reference-count":68,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T00:00:00Z","timestamp":1677456000000},"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>Therapeutics, based on small interfering RNA (siRNA), have demonstrated tremendous potential for treating cancer. However, issues such as non-specific targeting, premature degradation, and the intrinsic toxicity of the siRNA, have to be solved before they are ready for use in translational medicines. To address these challenges, nanotechnology-based tools might help to shield siRNA and ensure its specific delivery to the target site. Besides playing a crucial role in prostaglandin synthesis, the cyclo-oxygenase-2 (COX-2) enzyme has been reported to mediate carcinogenesis in various types of cancer, including hepatocellular carcinoma (HCC). We encapsulated COX-2-specific siRNA in Bacillus subtilis membrane lipid-based liposomes (subtilosomes) and evaluated their potential in the treatment of diethylnitrosamine (DEN)-induced hepatocellular carcinoma. Our findings suggested that the subtilosome-based formulation was stable, releasing COX-2 siRNA in a sustained manner, and has the potential to abruptly release encapsulated material at acidic pH. The fusogenic property of subtilosomes was revealed by FRET, fluorescence dequenching, content-mixing assay, etc. The subtilosome-based siRNA formulation was successful in inhibiting TNF-\u03b1 expression in the experimental animals. The apoptosis study indicated that the subtilosomized siRNA inhibits DEN-induced carcinogenesis more effectively than free siRNA. The as-developed formulation also suppressed COX-2 expression, which in turn up-regulated the expression of wild-type p53 and Bax on one hand and down-regulated Bcl-2 expression on the other. The survival data established the increased efficacy of subtilosome-encapsulated COX-2 siRNA against hepatocellular carcinoma.<\/jats:p>","DOI":"10.3390\/molecules28052191","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T03:23:36Z","timestamp":1677468216000},"page":"2191","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Potential of siRNA-Bearing Subtilosomes in the Treatment of Diethylnitrosamine-Induced Hepatocellular Carcinoma"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3072-7783","authenticated-orcid":false,"given":"Fauzia","family":"Jamal","sequence":"first","affiliation":[{"name":"Interdisciplinary Biotechnology Unit (IBU), Aligarh Muslim University, Aligarh 202002, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghufran","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Division of Microbiology, ICMR-Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Farazuddin","sequence":"additional","affiliation":[{"name":"Interdisciplinary Biotechnology Unit (IBU), Aligarh Muslim University, Aligarh 202002, India"},{"name":"Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, MI 48109-1316, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ishrat","family":"Altaf","sequence":"additional","affiliation":[{"name":"Interdisciplinary Biotechnology Unit (IBU), Aligarh Muslim University, Aligarh 202002, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saba","family":"Farheen","sequence":"additional","affiliation":[{"name":"Interdisciplinary Biotechnology Unit (IBU), Aligarh Muslim University, Aligarh 202002, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0284-4974","authenticated-orcid":false,"given":"Qamar","family":"Zia","sequence":"additional","affiliation":[{"name":"Interdisciplinary Biotechnology Unit (IBU), Aligarh Muslim University, Aligarh 202002, India"},{"name":"Health and Basic Science Research Centre, Majmaah University, Majmaah 11952, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9884-7645","authenticated-orcid":false,"given":"Asim","family":"Azhar","sequence":"additional","affiliation":[{"name":"Interdisciplinary Biotechnology Unit (IBU), Aligarh Muslim University, Aligarh 202002, India"},{"name":"Neat Meatt Biotech Private Limited, Bio-NEST-UDSC, University of Delhi (South Campus), New Delhi 110021, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hira","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Zoology, Aligarh Muslim University, Aligarh 202002, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aijaz Ahmed","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh 202002, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satyanarayana","family":"Somavarapu","sequence":"additional","affiliation":[{"name":"UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anshu","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Division of Basic and Clinical Immunology, Department of Medicine, University of California Irvine, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Owais","sequence":"additional","affiliation":[{"name":"Interdisciplinary Biotechnology Unit (IBU), Aligarh Muslim University, Aligarh 202002, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/s41575-019-0186-y","article-title":"A global view of hepatocellular carcinoma: Trends, risk, prevention and management","volume":"16","author":"Yang","year":"2019","journal-title":"Nat. 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