Tumor receptor-targeted nanoparticle containing a siRNA DNA cassette for the knockdown of survival genes and treating cancer.
- Nanoparticles are targeted directly to tumors for treatment and/or diagnostic imaging.
- siRNA encoded by a DNA cassette has increased stability and more effective gene depletion.
- siRNA knockdown of survival genes increases susceptibility to chemotherapy.
- Can be used alone or combined/incorporated with chemotherapeutics.
Cancer is the second leading cause of death in the United States and while cancer survival rates have increased so has cancer incidence. In the United States, over $100 billion is spent annually on cancer care and this number is expected to increase significantly in the following years due to an aging population and advances in early diagnostics. Although survival rates have increased, there are still challenges with one-size-fits-all cancer treatments. Traditional chemotherapy and radiation treatments are delivered to the whole patient resulting in severe side effects. In addition, the most life threatening and aggressive cancers frequently develop a resistance to chemotherapy treatments, specifically due to the increased expression and/or signaling of survival genes.
In order to more effectively treat chemotherapy resistant cancers, Emory researchers have developed an individualized technology that reduces the expression of survival genes. More specifically, they have developed theranostic nanoparticles which can be used to image tumor tissue and treat various cancers. This technology utilizes three interchangeable parts: a targeting ligand, nanoparticle, and cargo. The targeting component, a ligand for a receptor specifically expressed by tumor cells, ensures nanoparticles are specifically delivered to cancer tissue. Nanoparticles are either quantum dots or iron oxides, which can be imaged optically or by magnetic resonance imaging (MRI), respectively. Specifically of interest, the cargo can consist of a DNA cassette which encodes a siRNA against a tumor survival gene. Using a DNA cassette as opposed to a siRNA directly conjugated to the nanoparticles increases the stability of the genetic material leading to further reduction in gene expression in vitro and in vivo. Moreover, the reduction of survival gene expression reduces tumor cell proliferation and increases cell death in response to chemotherapy treatment. Nanoparticles containing the siRNA DNA cassette can be either used alone or in tandem with those containing chemotherapy drugs to reduce side effects and improve effectiveness.
In vitro and in vivo mouse xenograft datasuggest that these nanoparticles can silence gene expression in tumor cells and in human tumors growing in mice.
Publications: Cho, YS et al. (2013) Small, doi: 10.1002/smll.201201973
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