Delivery of Nucleotides for Gene Silencing of Cancer-Promoting Genes in Breast Cancer Cells



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Gene silencing through RNA interference (RNAi) is a common tool for cancer therapy via the delivery of siRNA. While this siRNA is effective at knocking down genes, a problem arises due to the inability of siRNA to enter the cell cytosol on its own. Many delivery agents are cytotoxic and inefficient, and dosing high amounts of siRNA can be toxic as well. We used nanoparticlestabilized capsules (NPSCs) to overcome the cytotoxicity and entrapment problems associated with common delivery agents. The gene of interest to be knocked down was hormonally up-regulated neu-associated kinase (Hunk), which is a gene expressed in HER2 cancer subtype, downregulates tumor suppressors, and is involved in metastasis. NPSCs were synthesized with anti-Hunk siRNA and/or lapatinib, a HER2 inhibitor. It was discovered that NPSCs with anti-Hunk siRNA effectively silences Hunk, shown by expression levels post-treatment, and cell viability decreases after treatment. Lapatinib NPSCs did not decrease Hunk expression, but did decrease viability. In the future, studies will aim to observe lapatinib’s effects at lower concentrations, tumor suppressor protein levels, and additive effects of dosing with multiple siRNAs or drugs in the same capsule complex.



Nanoparticle, Nanocapsule, Gene silencing, Lapatinib, Cancer, Hunk, Arginine