Bakhtiar, Athirah

Chowdhury, Md Ezharul Hoque

Kamaruzman, Nur Izyani

Othman, Iekhsan Bin

Zain, Dato’ Anuar Zaini Md

Genetic manipulation of cancer cells through intracellular delivery of plasmid DNA (pDNA) and short-interfering RNA (siRNA) would be an attractive approach for effectively treating various cancers with minimal adverse effects. However, naked DNA or siRNA is rapidly degraded by nucleases and exhibits low cellular uptake with resultant poor transfection efficiency. Recent studies have been focused on developing smart nanoparticles for efficient transport of transgenes and siRNAs into cancerous cells. The reaction between two soluble salts leading to precipitation of an insoluble salt in the form of particles has emerged as an excellent method to fabricate biocompatible nanocarriers with potential applications in gene therapy. Here, we report on development of nano-size particles based on insoluble barium salts having the capacity of adsorbing negatively charged plasmid DNA and siRNA and effectively carrying them into human (MCF-7) and murine (4T1) breast cancer cell lines. Inparticular, barium sulfate, barium sulfite and barium fluoride nanoparticles demonstrated strong binding affinity to nucleic acids, efficient cellular uptake and high transgene expression with low cytotoxicity in both cell lines. Intracellular delivery of siRNA targeting MAPK with the nanoparticles caused silencing of the MAPK gene particularly in MCF-7, leading to suppression of expression and activation MAPK and AKT, two key signaling molecules in MAPK and PI-3 kinase pathways, respectively. Moreover, nanoparticles-facilitated transport p53 genes into MCF-7 and 4T1 cellsresulted in significant cell death depending on the type of barium salt particles employed to carry the plasmid DNA. Therefore, barium salt nanoparticles have emerged as an attractive group of nanocarriers having tremendous prospect for efficient intracellular delivery of nucleic acid-based therapeutics to treat breast cancers

Intracellular Delivery of p53 Gene and MAPK siRNA into Breast Cancer Cells utilizing Barium Salt Nanoparticles

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