Ultrastable Nontoxic RNA Nanoparticles for Targeting Triple-Negative Breast Cancer Stem Cells
Technical Report,15 Mar 2015,14 Mar 2016
University of Kentucky Lexington United States
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While the underlying biological mechanisms of TNBC has been unraveled to a large extent over the last decade, effective strategies to deliver therapeutics to cancer cells in vivo has remained a great challenge. We recently discovered a phi29 pRNA three-way junction 3WJ motif with unusually robust properties that can be used as a scaffold to construct a new generation of drugs composed purely of RNA. Our goal is to apply our innovative non-toxic and non-immunogenic RNA constructs with specific TNBC targeting capability to deliver high doses of therapeutic payloads to the cancer cells with little orno collateral damage to healthy tissues. We have demonstrated that the RNA nanoparticles harboring EGFR aptamer and anti-miR21 sequence accumulated specifically in tumor sites in orthotopic TNBC xenografts after systemic injection, with little or no accumulation in health organs or tissues 8 hours post injection. The RNA nanoparticles were found to successfully inhibit the tumor growth in vivo. The results demonstrated that the pRNA-3WJ nanoparticles can be applied for clinical applications as a therapeutic gene delivery system to meet the urgent need of efficient strategies for the treatment of breast cancer.