| Autor: |
Jamal F; Interdisciplinary Biotechnology Unit (IBU), Aligarh Muslim University, Aligarh 202002, India., Ahmed G; Division of Microbiology, ICMR-Rajendra Memorial Research Institute of Medical Sciences, Patna 800007, India., Farazuddin M; Interdisciplinary Biotechnology Unit (IBU), Aligarh Muslim University, Aligarh 202002, India.; Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, MI 48109-1316, USA., Altaf I; Interdisciplinary Biotechnology Unit (IBU), Aligarh Muslim University, Aligarh 202002, India., Farheen S; Interdisciplinary Biotechnology Unit (IBU), Aligarh Muslim University, Aligarh 202002, India., Zia Q; Interdisciplinary Biotechnology Unit (IBU), Aligarh Muslim University, Aligarh 202002, India.; Health and Basic Science Research Centre, Majmaah University, Majmaah 11952, Saudi Arabia., Azhar A; Interdisciplinary Biotechnology Unit (IBU), Aligarh Muslim University, Aligarh 202002, India.; Neat Meatt Biotech Private Limited, Bio-NEST-UDSC, University of Delhi (South Campus), New Delhi 110021, India., Ahmad H; Department of Zoology, Aligarh Muslim University, Aligarh 202002, India., Khan AA; Department of Anatomy, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh 202002, India., Somavarapu S; UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK., Agrawal A; Division of Basic and Clinical Immunology, Department of Medicine, University of California Irvine, Irvine, CA 92697, USA., Owais M; Interdisciplinary Biotechnology Unit (IBU), Aligarh Muslim University, Aligarh 202002, India. |
| Abstrakt: |
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-α 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. |
