COX-2 siRNA encapsulated Liposome mediated suppression of angiogenesis: an enhanced anti-cancerous potential against Hepatocellular carcinoma murine model
Shadab Kazmi1, Asim Azhar1, Syed Mohd Faisal1, Swaleha Zubair, Mohammad Owais1
1Molecular Immunology & Nanovaccine Lab, Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, India-202002; 2Womens College, Aligarh Muslim University, Aligarh, India-202002
Post RNAi era, small interfering RNA (siRNA) based therapeutics seem to have tremendous scope in treatment of various incurable diseases including cancer. However, non-specific targeting, premature degradation and targeted delivery have before exploiting this wonderful approach in reality in translational medicines, issues like to be resolved. To address these challenges, nanotechnology based tools could be one plausible solution for siRNA shielding as well as specific delivery to the target site. Besides playing crucial role in prostaglandin synthesis, COX-2 (Cyclo-oxygenase 2) has been reported to mediate carcinogenesis and angiogenesis in various cancer types including hepatocellular carcinoma (HCC) as well. We encapsulated COX-2 specific siRNA template in Bacillus subtilis lipid based liposome (subtilosomes) and evaluated their potential in treatment of DEN-induced hepatocarcinogenesis. Our findings corroborated that subtilosomes are more stable, released COX-2 siRNA in a sustained manner and inhibited TNF-α expression more efficiently. Apoptosis measurement via APO-Brdu staining indicated that subtilosomized siRNA inhibits DEN-induced carcinogenesis much effectively when compared to free siRNA. The novel formulation inhibited COX-2 expression that in turn resulted in upregulation of p53 wild-type and Bax on one hand and downregulation of Bcl-2 expression on the other. Histopathology of liver tissues and survival data established that subtilosomal delivery of COX-2 siRNA helps in tumor regression, maintenance of morphology of hepatic cells, and increase in the survival of treated animals.
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