Nanoformulation of siRNA silencing Bcl-2 gene and its implication in cancer therapy

• Published in: Arzneimittel-Forschung Vol. 61; no. 10; p. 577
• Main Authors: Jagani, Hitesh Vitthalbhai, Josyula, Venkata Rao, Hariharapura, Raghu Chandrashekar, Palanimuthu, Vasanth Raj, Gang, Sagar Shanti Mal
• Format: Journal Article
• Language: English
• Published: Germany 01.01.2011
• Subjects: Animals; Blotting, Western; Cell Line, Tumor; Coloring Agents; Drug Compounding; Drug Delivery Systems; Electrochemistry; Female; Fluorescent Antibody Technique; Gene Silencing - drug effects; Genes, bcl-2 - genetics; Genetic Therapy; Humans; Lactic Acid; Male; Mice; Nanoparticles; Neoplasms - therapy; Particle Size; Polyglycolic Acid; Reverse Transcriptase Polymerase Chain Reaction; Rhodamines; RNA, Small Interfering - administration & dosage; RNA, Small Interfering - chemistry; RNA, Small Interfering - pharmacology; Tetrazolium Salts; Thiazoles; Transfection
• ISSN: 0004-4172
• DOI: 10.1055/s-0031-1300556

The purpose of this research work was to prepare poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles for delivery of siRNA (small interfering RNA) for silencing anti-apoptotic Bcl-2 gene in cancerous cells by using the double emulsion solvent diffusion (DESE) method. Overexpression of Bcl-2 is often seen in a wide variety of human cancers. This prevents the induction of programmed cell death (i.e., apoptosis) in cancerous cells. It is also reported that over-expression of Bcl-2 contributes to resistance in chemotherapy and inhibits the apoptosis induced by chemotherapeutic agents. Agents antagonizing the anti-apoptotic Bcl-2 protein have been shown to restore normal apoptotic processes in cancer cells. RNA interference (RNAi) has emerged as an efficient and selective technique for gene silencing, siRNA mediated gene silencing has been used in a wide variety of disease condition. PLGA nanoparticles were able to completely bind siRNA and to provide protection for siRNA against nuclease degradation. In vitro cell culture studies subsequently revealed that PLGA nanoparticles with adsorbed siRNA could efficiently silence the targeted anti-apoptotic Bcl-2 gene in mammalian cells. In vivo studies results showed that siRNA was effectively delivered through nanoparticles and there was significant decrease in the tumor volume.